Paediatric acute haemorrhagic leukoencephalitis

Background

Acute haemorrhagic leukoencephalitis (AHLE), also known as Weston Hurst syndrome, is a rare hyperacute variant of acute disseminated encephalomyelitis (ADEM) characterised by severe, rapidly progressive clinical illness and diffuse haemorrhagic necrosis of white matter.1 ADEM and AHLE represent two clinical variants of demyelinating disease spectrum with the former being more common in children with favourable outcomes and the latter being rare, and more prevalent in young adults with the fulminant course and high mortality. The definitive aetiology of AHLE is not well defined but antecedent upper respiratory tract infections support the hypothesis of an autoimmune process based on molecular mimicry.2

Since Hurst described the first case in 1941, the total number of reported cases has remained under 100 in 75 years, with most mentioning very high mortality.3 4 The ideal management of this condition is debatable, but aggressive immunosuppressive regimens are mostly recommended. Because there is scarce literature on AHLE management in the paediatric population, we are reporting this case to heighten awareness about effective management. Our case is unique in a way that despite the hyperacute onset, and rapid deterioration with a stormy course in the intensive care unit (ICU), the child survived with good recovery and no neurological sequelae. We conclude that although AHLE is known to be usually fatal, early recognition, aggressive immunosuppression and prompt rehabilitation can increase the odds of survival.

Case presentation

A previously healthy preschool age girl was referred to our paediatric ICU from another city hospital on ventilatory support. The child presented to the city hospital with a 1-day history of projectile vomiting and headache with abrupt onset of neurological symptoms in the form of diminished vision followed by three episodes of generalised tonic seizures lasting 5–10 min with the loss of consciousness. She had no history of antecedent upper respiratory infections, diarrhoea, conjunctivitis, arthralgia or rash. There was no history of recent travel, trauma or vaccinations. The child was ventilated in the outside hospital because of poor Glasgow Coma Scale (GCS), received intravenous antibiotics (ceftriaxone, linezolid) and antivirals (acyclovir), osmotherapy with mannitol and 3% saline and after 10 days of hospital stay with no signs of neurological improvement, she was referred to our tertiary care facility

On admission, the patient was febrile (temperature ~39.4°C); pulse 120 beats/min; blood pressure 106/68 mm Hg and oxygen saturation was 90% on assisted ventilation with no spontaneous respiratory efforts. She was deeply comatose with GCS of 3/15 and absent brainstem reflexes. Her pupils were dilated and non-reactive. She had flaccid quadriplegia with mute deep tendon reflexes and an upgoing plantar response. Cranial nerve examination revealed absent ocular movements, absent corneal, gag and doll’s eye reflex. There were no signs of meningitis and papilledema was absent. Respiratory examination revealed decreased air entry on the left side with coarse crepitations. Abdomen and cardiovascular examinations were within normal limits.

Differential diagnosis

Based on initial clinical presentation, wider differentials including stroke, meningoencephalitis, fulminant demyelinating diseases-like ADEM and its variant AHLE, febrile infection-related epilepsy syndrome (FIRES), neuromyelitis optica (NMO)-spectrum disorders associated with aquaporin autoimmunity and cranial nervous system vasculitides were considered. NMO spectrum disorders were ruled out based on negative anti-aquaporin-4 antibody and myelin oligodendrocyte glycoprotein antibodies. The EEG was not suggestive of FIRES. The results of antinuclear antibodies, inflammatory markers, lipid profile and urine analysis were normal, hence the diagnosis of vasculitis was unlikely. Correlating with the clinical scenario, radiological differential diagnoses included parainfectious demyelinating aetiologies like haemorrhagic ADEM and haemorrhagic meningoencephalitis. CSF analysis showed no evidence of infection and absent meningeal enhancement on neuroimaging excluded infectious causes of meningoencephalitis. The diagnosis of AHLE was made based on the acute fulminant course of the disease and radiological findings but there was no histopathological examination performed to confirm it.

Treatment

At presentation, the child was in respiratory failure with shock, encephalopathy and multiorgan dysfunction syndrome. She was managed with mechanical ventilation, antibiotics, inotropic support and blood products. Pulse therapy with intravenous methylprednisolone (30 mg/kg/day) was initiated, considering the neuroimaging possibility of AHLE. However, there were no signs of clinical improvement even after 5 days of methylprednisolone, hence, therapeutic plasma exchange was initiated. After the first cycle of plasmapheresis, the child showed some improvement like saccadic eye movements and blinking along with spontaneous respiratory efforts and gag reflex. Five cycles of alternate day plasmapheresis were completed. On account of persistent respiratory failure, poor GCS and failure to wean off, tracheostomy was done on day 11 of the PICU stay. Since the child did not show any further clinical improvement, intravenous immunoglobulin (2 g/kg over 2 days) was given on day 14 of stay. The child was continued on oral prednisolone at 1 mg/kg/day. The child was managed with appropriate antibiotics for ventilator-associated pneumonia. She was put off ventilatory support on day 40 with tracheostomy tube in situ. She was then shifted to the ward and aggressive rehabilitation continued. Decannulation was done after 2 months of hospital stay.

Outcome and follow-up

After a month of ICU stay, the patient’s neurological condition improved gradually. The child began communicating with eye gestures and orofacial movements, muscle strength gradually increased to 2/5 in all four limbs, superficial and deep tendon reflexes were regained, and emotional responses appeared. After 2 months of hospitalisation, the child at discharge had improved muscle strength of 3/5 in arms and 2/5 in lower extremities, reactive pupils with no gross cranial nerve deficit and good oral intake. The child regained nearly full strength 3 months after the initial presentation. The girl has no neurological sequelae and has recovered completely after a year of follow-up . On detailed neurological examination, she has muscle strength of 5/5 in all four limbs with normal tone and deep tendon reflexes. Her gait and spine are normal. There is no evidence of spasticity or contractures. She has no trouble performing age-appropriate chores.