A rare cause of neonatal hydrocephalus

Introduction

Neonates are often referred as a result of jaundice and poor feeding. In our case, the neonate was found to have hydrocephalus secondary to a posterior fossa haemorrhage. The diagnosis of haemophilia was made later. This case shows the importance of considering rarer diagnosis with common presentations and the need for acute imaging to aid management.

Case report

A term male infant was born by vaginal delivery in a birthing pool, following an uneventful labour and pregnancy. At birth, he did not require resuscitation and there was no cephalhaematoma or bruising. He was discharged home having received vitamin K and breast feeding. His 34-year-old mother had one healthy female child and there was no relevant family history. He was referred to the hospital on day 3 with jaundice, weight loss, and poor feeding. On admission, he was hypotonic with limited antigravity movements. Antibiotics were commenced and a neurometabolic screen initiated. Full blood count and biochemistry were normal, with coagulation screen reported as “clotted”. Cranial ultrasound showed moderate lateral and third ventricular dilatation, with no visible fourth ventricle and no blood clot in the ventricular system. He had a clinical seizure 12 h after admission, confirmed on two-channel electroencephalography (EEG), which was treated with phenobarbitone.

On examination, he had a tense fontanelle and was hypertensive (mean arterial blood pressure 86 mm Hg). Repeat cranial ultrasound confirmed ventricular dilatation and Doppler of the anterior cerebral artery showed absent diastolic flow, confirming markedly raised intracranial pressure (Figure 1). Lumbar tap yielded minimal blood stained fluid, however, direct ventricular puncture produced lightly blood stained cerebrospinal fluid (CSF) with opening pressure of over 50 cm H₂O. Following drainage of 40 mL of CSF, the pressure reduced to 16 cm H₂O and he clinically improved. Oozing was noted from puncture sites and repeat coagulation screen demonstrated activated partial thromboplastin time (APTT) >150 s (normal range 30 s–54 s), INR of 1.2 and prothrombin time (PT) of 12.4 s (normal range 10 s–16 s). Factor assays were performed with factor VIII levels of <1 IU/dL, confirming the diagnosis of severe haemophilia A. He was immediately started on replacement treatment with a recombinant B-domain deleted factor VIII. Pre- and post-administration factor VIII levels were measured to ensure adequate levels (>100 IU/dL).

Figure 1

Doppler waveforms from the anterior cerebral artery (A) before ventricular drainage, showing absence and occasional reversal of diastolic flow. Following ventricular drainage (B) there was restoration of diastolic flow and an overall improvement in the flow velocity profile.

Brain computed tomography showed a large bilateral posterior fossa subdural haemorrhage, with some haemorrhage into the cerebellum, effacing the fourth ventricle (Figure 2). Neurosurgical opinion was against acute surgery unless raised intracranial pressure reoccurred. His respiratory effort became inadequate and he required ventilation for 8 days. Axial hypotonia continued, however, he regained antigravity movements and there was no evidence of increasing intracranial pressure. Brain magnetic resonance imaging at 3 weeks of age showed minimal hydrocephalus and improvement in the subdural haematoma. Inhibitor screen was initially negative but became positive on day 18 and he received inhibitor eradication (immune tolerance induction). Recombinant activated factor VII (rFVIIa) was added to prevent further bleeding episodes. His neurology continued to improve and his 4 month developmental assessment was age appropriate, although his neurodevelopment will be monitored.

Figure 2

Computed tomography image at the level of the temporal lobes and posterior fossa. There is a large bilateral posterior fossa subdural haemorrhage, with some haemorrhage into the cerebellum, especially on the left side adjacent to the tentorium cerebelli, with complete effacement of the fourth ventricle. Dilated temporal horns of the lateral ventricles can also be seen.

Discussion

This neonate presented with symptoms of acute hydrocephalus from a posterior fossa haemorrhage causing effacement of the fourth ventricle. The severity of the haemorrhage was probably related to underlying haemophilia A. Although bleeding problems are common in neonates, most occur in sick or prematurely born, as a result of thrombocytopenia or disseminated intravascular coagulation. Immature neonatal coagulation pathways include variability in haemostatic protein concentrations, however, these rarely cause clinical problems in healthy newborns. Inherited disorders often manifest in otherwise healthy babies. A prolonged APTT indicates abnormalities in clot formation, and tests for factors VIII, IX, X, and XI. The normal PT excluded an activated sample, or the presence of coagulopathy from sepsis. The normalisation of APTT with addition of normal plasma confirmed the lack of a clotting factor and the absence of an inhibitor antibody.

Haemophilia A (factor VIII deficiency) and B (factor IX deficiency) are the most common inherited neonatal clotting deficiencies. Haemophilia A occurs in 1 in 10,000 births [5] in all racial groups. It is classified by factor VIII level (as percentage of normal): mild (>5–<40 IU/dL), moderate (1–5 IU/dL), and severe (<1 IU/dL). Inhibitors are IgG antibodies that neutralise clotting factors. The risk of developing inhibitors in severe haemophilia is 20–30% [5]. Risk factors for developing inhibitors include genetic factors, a family history of developing inhibitors, ethnicity, treatment factors such as age at first exposure and the intensity of exposure to factor concentrates [1]. The factor VIII gene locus is at Xq28, thus, the majority are male, although carrier females sometimes develop bleeding as a result of lyonization. At least one third lack a family history [5].

Whilst many haemophilia newborns have an uneventful vaginal delivery, a recent European study concluded that assisted vaginal delivery via forceps or vacuum procedures should be avoided in mothers known to be haemophilia carriers [4]. Newborns may present with haemorrhage after blood taking or the vitamin K injection, subgaleal or cephalo-haematomas, intracranial haemorrhage, haematuria or retro-orbital bleeding. Major bleeding is relatively uncommon, but cranial bleeding is more likely in the first few days of life. Studies of the incidence of symptomatic intracranial haemorrhage in well neonates with haemophilia have ranged from 1.9% [6] to 4% (40–80 times higher than in the normal population) [2]. Radiological studies have shown a much higher than expected prevalence of asymptomatic intracranial haemorrhage in term well neonates of 26% [3]. In our patient, the clinical effects were probably mediated through an acute obstructive hydrocephalus secondary to effacement of the fourth ventricle. Acute decompression was required as intracranial pressure exceeded diastolic blood pressure and was dangerously close to systolic blood pressure. Fortunately there was no bleeding along the track of the puncture, especially as this was required in an acutely decompensating baby before coagulation studies were available.

This case shows the importance of investigation for coagulation abnormalities in any neonate with a deteriorating level of consciousness. Localised posterior fossa haemorrhage is easily missed on cranial ultrasound and a “clotted” coagulation specimen does not exclude major coagulation disorders. Consideration should be given to more advanced neuroimaging for hydrocephalus, especially as cranial ultrasound scans are not as sensitive for posterior fossa localisation. A small posterior fossa haemorrhage may produce acute obstructive hydrocephalus, with life-threatening raised intracranial pressure but only modest dilatation of the ventricles.