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Pathways of neonatal stroke and subclavian steal syndrome
  1. L M Beattie1,
  2. S J Butler2,
  3. D E Goudie3
  1. 1Paediatric Department, Queen Mother’s Hospital, Dalnair Street, Glasgow G3 8SJ, Scotland, UK
  2. 2Department of Radiology, Royal Hospital for Sick Children, Dalnair Street, Glasgow G3 8SJ, Scotland, UK
  3. 3Department of Paediatrics, Raigmore Hospital, Old Perth Road, Inverness IV2 3UJ, Scotland, UK
  1. Correspondence to:
    Dr Beattie
    Paediatric Department, Queen Mother’s Hospital, Dalnair Street, Glasgow G3 8SJ, Scotland, UK; lynne_beattie{at}hotmail.com

Abstract

Neonatal stroke may occur silently. Identification of potential embolic pathways unique to the neonate is important when investigating the aetiology of infarction and arterial occlusion, and preventing further episodes. This is a case report of an infant with venous thrombus embolising across the foramen ovale causing cerebral infarction and subclavian artery steal syndrome, without neurological signs.

  • ADC, apparent diffusion coefficient
  • IVC, inferior vena cava
  • LAC, lupus anti-coagulant antibody
  • MCA, middle cerebral artery
  • MRA, magnetic resonance arteriography
  • PFO, patent foramen ovale
  • stroke
  • steal syndrome
  • patent foramen ovale
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The incidence of arterial ischaemic stroke in the neonatal period is reported to vary from 93 per 100 000 live births in the Canadian Registry1 to 1 in 4000 live births per year from reports published by Estan and Hope and the Report of the National Institute of Neurological Disorders.2,3 Most neonates with stroke present with seizures or hypotonia, but a minority present after the neonatal period with progressive neurological signs.4 Some remain without abnormal neonatal signs, and whether or not they have acquired the infarct antenatally is often difficult to tell. Naturally, the true incidence of silent infarction is unknown. Neonates with cerebral thromboembolism can be seen to have a high rate of prothrombotic risk factors.5 In the presence of venous thrombosis, identification of potential embolic pathways unique to the neonate is paramount, even in the absence of neurological symptoms.

CASE REPORT

A healthy 25 year old woman had a normal pregnancy, with routine ultrasound scans revealing no thrombi or cerebral concerns. Before this pregnancy, she had experienced a miscarriage at seven weeks. Her routine booking bloods in this second pregnancy were normal, and neither she nor her partner had any personal or family history of haematological disorder. Labour was induced at 37 weeks and 5 days because of maternal pregnancy induced hypertension. Maternal pre-eclampsia and a “non-reassuring” cardiotocograph indicating possible fetal distress necessitated an emergency caesarean section the following day. A female infant was delivered in good condition, without need for resuscitation. She weighed 3140 g (50th centile for gestational age) and had an occipitofrontal circumference of 34 cm (also 50th centile for gestational age). With Apgar scores of 9 at one minute and 10 at five minutes, she was immediately reunited with her mother. On examination, the newborn was non-dysmorphic and without any concerning features.

At 33 hours of age she was admitted to the neonatal unit with jaundice and “poor feeding”. The latter entailed having to be woken for breast feeds, but she had a normal suck. She was normally rousable, with normal tone, power, and reflexes in all limbs. Normal primitive reflexes were present. Soon after admission, oozing from venesection sites and fresh rectal bleeding were noted, and her platelet count was 30 × 109/l. She was transfused with platelets accordingly. Notably, she reacted normally to pain stimuli at venesection and peripheral cannulation. During days 3 and 4, she remained well, maintaining a normal platelet count. On day 5 her right leg became dusky and swollen, with reduced pulses. Doppler ultrasound revealed reduced velocity in the right common and superficial femoral veins, but normal arterial flow. She was transferred to The Queen Mother’s Hospital neonatal unit that day for further assessment. Importantly, at no time did she develop seizures, posturing, or abnormal neurological signs.

An echocardiogram on day 5 of life revealed normal cardiac anatomy with left to right flow across the foramen ovale and a “shadow” in the inferior vena cava (IVC) suggesting thrombus. The subclavian arteries were examined and noted to be patent with normal flow. Abdominal ultrasound on the same day confirmed IVC thrombus from the liver to the iliac bifurcation, extending into the right common iliac vein. With the potential for paradoxical embolism, a cranial ultrasound was performed on the same day, and showed echogenicity in the left temporoparietal region consistent with a left middle cerebral artery (MCA) territory infarct. A computed tomographic brain scan immediately after ultrasonography confirmed the incomplete left MCA territory infarct with extension into posterior cerebral artery territory. No haemorrhage was identified. Magnetic resonance brain scan including magnetic resonance arteriography (MRA) of the intracranial vessels on day 6 confirmed these findings (figs 1–4). MRA showed a normal patent Circle of Willis and vertebrobasilar system. In particular, the left vertebral artery on the inferior aspects of the MRA showed normal caudocranial direction of flow.

Figure 1

 Axial image map of the apparent diffusion coefficient (ADC); a summation of the three different diffusion weightings used, obtained at day 6. Restricted diffusion due to cytotoxic oedema in an acute infarct is manifested as low ADC (low signal) as shown. The ADCs are higher in the neonatal white matter, hence the relative increased signal intensity. As this is the ADC map of the diffusion sequence, brain anatomy is poorly differentiated.

Figure 2

 On this T2 axial sequence, abnormal increased signal is present in the posterior one third of the left posterior limb of the left internal capsule. There is loss of grey-white matter differentiation in the left middle and posterior cerebral artery territories, consistent with infarction. This corresponds to the abnormal area on the ADC map (fig 1).

Figure 3

 This inversion recovery T1W sequence shows some increased signal intensity peripherally in the left lentiform nucleus, but the remainder of the ipsilateral basal ganglia and thalamus are otherwise unaffected. This area of increased signal intensity is believed to be the demarcation zone between affected and unaffected brain. An area of relatively low signal intensity on the T2W sequence denotes this area.

Figure 4

 An inversion T1 recovery axial of the brainstem.

On day 7, she developed a pulseless left arm. Perfusion, however, remained satisfactory. In light of this, a repeat echocardiogram was performed which identified thrombus in the left subclavian artery, and some physiological bidirectional flow across the patent foramen ovale (PFO). No pulmonary hypertension or emboli were noted, there was no right ventricular outflow tract obstruction or pulmonary stenosis, and she remained well saturated. At this point, as her arm remained well perfused, a decision was taken not to administer fibrinolytic or thrombolytic therapy because of the risk of haemorrhage. She remained neurologically normal. In deference to this, an electroencephalogram was not obtained. Constant cardiovascular and respiratory monitoring was normal. On day 10, two dimensional time of flight arteriography and venography of the major neck and mediastinal vessels showed reversed flow in the left vertebral artery consistent with subclavian steal syndrome (figs 5 and 6).

Figure 5

 Two dimensional time of flight axial venogram image of the neck, set up to show blood flow from the head, in a caudal direction down through the neck. A saturation band is applied inferiorly to saturate arterial flow from below. The image shows normal craniocaudal flow in the internal jugular veins and abnormal direction of blood flow in the left vertebral artery. The structure posterior to the left internal jugular vein is the left vertebral artery showing similar direction of flow—that is, reversed for the vertebral artery.

Figure 6

 Two dimensional time of flight angiogram of the neck, with a saturation band applied superior to the imaging plane to saturate venous flow from the head, shows normal direction of flow in the right vertebral and both common carotid arteries and absent signal in the left vertebral artery. This is due to abnormal flow direction.

Tertiary neurology opinion was sought to ascertain whether the risk to cerebral perfusion was high enough to merit angioplasty of the affected subclavian artery segment. It was felt, however, that the risk of distal limb embolism during the procedure was considerably higher than any compromise to the vertebrobasilar circulation, thus angioplasty did not occur. Thrombolytic or fibrinolytic therapy was reserved in the event of IVC or subclavian arterial clot extension. The subclavian thrombus was indeed noted on ultrasound on day 8 to have extended, and low molecular mass heparin was started. Her arm, although pulseless, remained well perfused and she had a normal neurological examination. Thereafter, should any further cerebral emboli have occurred, closure of the PFO would have been entertained.

By day 15 of life, she was stable, without further thromboemboli or neurological concern. The mother was subsequently shown to be lupus anticoagulant antibody (LAC) positive, although studies for the baby are negative to date. In addition, all metabolic and microbiological investigations were negative. She remained well for the rest of the neonatal period, without neurological concern. Her arm remained well perfused and both IVC and subclavian thrombi were seen to rescind on serial ultrasound over the following six months. She continued to receive low molecular mass heparin for six months. Subsequent developmental assessment at 13 weeks, however, identified a dense right sided hemiplegia.

DISCUSSION

The perinatal period is a time of heightened risk for stroke in mother and baby, in response to the physiological activation of coagulation factors.6 LAC is an antibody to phospholipid that inhibits the prothrombin activator complex, paradoxically causing thrombosis. Venous thrombosis, stroke, and miscarriage are known to be more common in women carrying these autoantibodies. Maternal LAC is associated with an increased risk of intrauterine growth retardation, probably secondary to a vasculopathy with placental insufficiency, rather than a direct effect on the fetus. Theoretically, LAC may cross the placenta, and there is only one known report of neonatal venous thrombosis and LAC, in conjunction with maternal LAC.7

An interatrial communication, the foramen ovale, remains patent after the neonatal period in about 35% of patients with normal cardiac anatomy.8 Closure is achieved secondary to the fall in pulmonary vascular resistance and increase in left heart pressure. Closure may therefore be functional, but not actual. The potential for paradoxical right to left flow of emboli at this level is little reported in the neonatal period, but can lead to cerebral infarction. One report outlined neonatal cases, all with neurological signs.9 Right to left flow can be physiological in response to the valsalva manoeuvre, which in infants may be stimulated by crying, coughing, or defecation.10 In adults, the valsalva manoeuvre is indeed used at the time of echocardiography to identify PFO.11 PFO closure is gaining in popularity to prevent further emboli and infarction.

Thrombus may also embolise via the PFO to the arterial circulation of the upper limbs. Subclavian steal syndrome is the occlusion or stenosis of the subclavian artery resulting in reversal of flow in the ipsilateral vertebral artery. This may lead to vertebrobasilar insufficiency and cerebral ischaemia.12 There are no published reports of neonatal subclavian steal syndrome. Where thrombus exists as the occluding component, angioplasty may be considered to recannulate. However, the risk of distal limb embolism from this procedure must be weighed against the perceived risk of vertebrobasilar hypoperfusion.

What is already known on this topic

  • The foramen ovale can remain patent in the neonatal period

  • Venous thrombus in the neonate can embolise across the patent foramen ovale to cause devastating cerebral infarction

What this study adds

  • Cerebral infarction may remain silent in the neonatal period, thus echocardiography, along with cranial imaging, should be considered essential in all cases of venous thrombus

  • Thrombus may also embolise to limb vessels via this portal, requiring vascular imaging to assess extent

It is important that the infant had no abnormal neurological signs before the diagnosis of cerebral infarction. It is our considered opinion that the MCA and posterior cerebral artery territory infarcts occurred in the first week of life, as the infarct is relatively subtle on conventional magnetic resonance sequences but is well demarcated on the diffusion weighted sequences and the ADC map (figs 2 and 3), along with effacement of the intervening sulcal spaces. In addition, the infarct is best demonstrated on the diffusion weighted images and the ADC map.13 Although some studies postulate that infants with antenatally acquired infarcts are less likely to incur abnormal neurological signs in the neonatal period, there are no other magnetic resonance features suggesting this in our patient. Reversal of flow across the PFO is then considered to have occurred physiologically, and temporarily, probably in response to a valsalva manoeuvre. IVC thrombus embolised to the intracranial arterial circulation causing cerebral infarction. Subsequent embolism to the left subclavian artery resulted in the subclavian steal syndrome. This recurred thereafter, as evidenced by extension of the subclavian arterial clot.

CONCLUSIONS

We suggest that all infants presenting with venous thrombosis should undergo echocardiography and cranial imaging in the first instance. Cranial ultrasound should occur even if the infant remains neurologically normal, and magnetic resonance brain, venography and arteriography should occur in the event of any neurological or ultrasound abnormalities.

Acknowledgments

We thank Dr Barbara Holland, Consultant Neonatologist at Queen Mother’s Hospital, and Dr Alan Houston, Consultant Cardiologist at the Royal Hospital for Sick Children, both Yorkhill, Glasgow.

REFERENCES

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Footnotes

  • Competing interests: none declared

  • Written consent was obtained from the mother.

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