P226 Iron deficiency anaemia and ischaemic stroke in children

Posters Conclusion: These data may allow stroke prevention as more patients with congenital heart disease survive. P225 Inherited leukoencephalopathy due to COL4A1 mutation presenting with two different phenotypes in the same family V. Murugan1 *, K. Lachlan2 , A. Whitney1 . 1 Southampton General Hospital, Southampton, United Kingdom; 2Wessex Regional Genetics Service, Southampton, United Kingdom Background: The role of mutations in the gene COL4A1 encoding collagen IVA1 has been highlighted as a cause of cerebral microangiopathy and porencephaly. Objective: We report two siblings diagnosed with a vascular leukoencephalopathy secondary to COL4A1 mutation. Method: Case reports of two brothers. Case 1: A 5-year-old boy was born by caesarian section for maternal pre-eclampsia at 35 weeks gestation. Bilateral congenital cataracts were diagnosed at 3 months of age and he subsequently developed an asymmetric four limb hypertonic motor disorder. Brain MRI at two-years of age demonstrated widespread, asymmetric, periventricular white matter hyperintensities. At the age of 4-years he presented with an acute neurological illness associated with bulbar dysfunction and generalised hypotonia. Repeat brain MRI demonstrated bilateral lacunar infarcts and a generalised leukoencephalopathy. Case 2: A 2-year-old sibling was diagnosed with rightsided hemiplegic cerebral palsy at 6 months of age, with a normal perinatal history. Brain MRI at 11 months of age demonstrated a left sided frontal porencephalic cyst with hyperintense periventricular white matter. Their mother was diagnosed with bilateral cataracts at birth. There is a strong family history of migraine. Both sibs have c.2317G>C (p.Gly773Arg) missense mutation in a highly conserved region of the COL4A1 gene. Discussion: COL4A1 mutations are associated with phenotypic diversity. Relatives of children with familial porencephaly have been reported to have increased risk of cerebral microbleeds and lacunar infarcts with associated leukoencephalopathy. In some families, retinal abnormalities are reported. Several distinct phenotypes have been reported, one of which with anterior eye chamber anomalies including cataract, leukoencephlopathy, ischaemic lacunar infarcts, and microbleeds would be in keeping with the presentation observed in our family. Conclusion: We report a novel mutation in the COL4A1 gene in a British family who presented with differing phenotypes. We suggest consideration of COL4A1 mutation in families with a history of motor disorder, cataract and migraine. P226 Iron deficiency anaemia and ischaemic stroke in children P. Munot1 *, C. DeVile1 , C. Hemingway1 , V. Ganesan1 . 1 Paediatric Neurology, Great Ormond street Hospital, London, United Kingdom Objective: To describe instances of ischaemic stroke in children with iron deficiency anaemia and discuss potential underlying mechanisms. Case descriptions: See the table. Discussion: Iron deficiency anaemia has previously been reported as a risk factor for both arterial and venous cerebral infarction in children; however the underlying mechanisms are not completely understood. Proposed mechanisms include thrombocytosis and reduced red cell deformability due to microcytosis both of which result in increased viscosity and secondary hypercoaguable state. Anaemia may also worsen regional hypoxia in areas of decreased

S91 perfusion and may alter local cerebral haemodynamics. These hypotheses are supported by the reversible turbulence in both MCAs seen in 1 of our patients and the abnormal platelet count and or function noted in 3 cases. Conclusion: Iron deficiency anaemia is a significant and preventable risk factor for childhood ischaemic stroke. Case 1

Case 2

Case 3

Case 4

Age Presentation

14 mo Acute L hemiparesis

24 mo Seizures, L hemiparesis

40 mo 2 weeks headache and vomiting

Hb (g/dl) at presentation Ferritin ug/L (normal 9.8−73) Platelet count (×109 /L) Range 150 450 Platelets on blood film

5.6

35 mo R focal seizures, R hemiparesis, papilloedema 5.6

Prothrombotic screen1 Other stroke risk factors Imaging

13

4.7

7.7

35 (Serum iron = 0.8 mmol/L)

5

376

257

1744

250

Reactive thrombocytosis with large platelet forms. Normal

Reactive thrombocytosis with platelet clumping. Normal

Reactive thrombocytosis

No comments on platelets

Normal

Normal

None

None

None

Otitis media

R middle cerebral artery territory (MCA) infarct. Turbulence in proximal R MCA secondary to anaemia (subsequently resolved)

Bilateral frontoparietal haemorrhagic infarction Dural venous sinus thrombosis

Bilateral venous infarcts Thrombosis of deep cerebral veins and straight sinus

Normal brain parenchyma Thrombosis in sagittal, transverse sinuses & internal jugular vein

1 Including Protein S, protein C, FVL, etc

P227 Multidisciplinary management of complex cerebrovascular disease in children V. Ganesan1,2 *, C. Devile2 , D.E. Saunders4 , D. Thompson3 , F. Robertson4 , S. Brew4 . 1 Neurosciences Unit, Institute of Child Health, UCL, London, UK; 2 Neurology Department, Great Ormond Street Hospital for Children NHS Trust; 3 Neurosurgery Department, Great Ormond Street Hospital for Children NHS Trust; 4 Radiology Department, Great Ormond Street Hospital for Children NHS Trust, UK Aim: To describe combined medical, surgical and endovascular management of a child with complex cerebrovascular disease. Case description: A 2 y 10 mo old boy presented with a generalised seizure and acute R hemiparesis. He was hypotonic at birth with macrocephaly, dysmorphic features and global developmental delay, but without a unifying diagnosis and normal brain imaging. Brain magnetic resonance imaging (MRI) showed acute infarction in the distribution of the R middle cerebral artery. The hemiparesis improved but he went on to have 2 further R sided events, with progressive L hemisphere infarction over the next 6 months. MR angiography showed occlusion of the terminal R internal carotid artery (ICA) and a focal tight stenosis of the L ICA just above the carotid bifurcation. Echocardiography, investigations for vasculitis and muscle biopsy were unrevealing; there was no unifying diagnosis. He was treated with aspirin but was anticoagulated after a further R sided event and ultimately underwent R pial synangiosis. There were no further R sided events thereafter and angiography showed good post-operative collateralisation. Anticoagulation was stopped. 18 months later he developed acute L hemiparesis lasting 5 days. MRI did not show R hemisphere injury but catheter cerebral angiography showed progression of the R ICA disease. In view of this and his symptoms a stent was inserted in the R ICA via an endovascular approach, with