nature of these risk factors confounds our ability to providecurrent perioperative care directed at maximizing neurode-velopmental outcomes. Hopefully, moving forward, morecomprehensive perioperative monitoring, including MRI,

near infrared spectroscopy to monitor mixed venous oxy-gen saturation, and EEG will better identify at-riskpatients and direct early interventions to improve long-term neurodevelopmental and quality of life outcomes.

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Hemiconvulsion-hemiplegia syndrome: new insights fromneuroimaging

LAURENCE J ABERNETHYDepartment of Radiology, Alder Hey Children’s NHS Foundation Trust, Liverpool,UK.

doi: 10.1111/dmcn.12235

This commentary is on the original article by Barcia et al. on pages1150–1158 of this issue.

Hemiconvulsion-hemiplegia syndrome (HHS) is a rare andsevere complication of prolonged unilateral convulsive statusepilepticus in young children. The initial seizure occurs in thecourse of a febrile illness and is followed by ipsilateral hemi-plegia. In many cases, epilepsy develops 1 to 3 years later,often characterized by partial seizures with secondary general-ization and episodes of status; this constitutes the hemicon-vulsion-hemiplegia-epilepsy (HHE) syndrome. In addition topartial epilepsy, most children who develop HHE have somedegree of cognitive impairment. The clinical syndrome wasfirst described over 50 years ago by Gastaut et al.,1 but thepathophysiology of HHS remains unclear and it is difficult topredict the long-term outcome in individual cases. Previousradiological studies2,3 have demonstrated that in the earlystages of HHS, magnetic resonance imaging (MRI) showsunilateral cerebral hemisphere swelling, with sulcal efface-ment and diffuse cortical and white matter hyperintensity onT2-weighted images. In the chronic phase, the acute changesare superseded by the development of cerebral atrophy andgliosis in the affected hemisphere.

Barcia et al.4 report 10 cases of this condition, withdescription of the MRI features, including advanced MRI(diffusion imaging and spectroscopy) in the acute phase.They demonstrate that early MRI in febrile status epilepti-cus can help to establish the diagnosis of HHS and showsmore frequent involvement of subcortical structures thanin previous studies. Diffusion-weighted imaging showsrestricted diffusion in the affected hemisphere, indicatingcytotoxic oedema. Preferential involvement of the posteriorpart of the affected cerebral hemisphere was evident in fivecases. Acute basal ganglia involvement was demonstratedin seven cases and hippocampal involvement in four. Hip-pocampal atrophy developed on subsequent imaging in fivepatients. MR angiography and spectroscopy were non-con-tributory in most cases.

CONTROVERSIESIt remains uncertain whether HHS is a single cohesivesyndrome rather than the result of a number of differentconditions that result in hemiplegia and a hemiseizure.Idiopathic HHS occurs in previously healthy children, and isassociated only with fever secondary to extracranial infec-tion, while the symptomatic type occurs in children with apre-existing neurological disorder, traumatic brain injury,coagulation disorders such as inherited protein S deficiency,or metabolic disorders such as L-2-hydroxyglutaric aciduria.In the cohort described by Barcia et al.,4 there were four chil-dren with pre-existing neurological conditions. Only two have

Commentaries 1073

subsequently developed epilepsy, fulfilling the criteria forHHE.

The cause of HHS remains unclear, but it is likely tobe multifactorial. Vascular and inflammatory mechanismshave been suggested. Clinical and radiological findingsindicate a characteristic sequence of events comprisingan initial prolonged focal seizure, unilateral cerebraloedema, progressing to cortical and subcortical atrophy.These changes could be caused by infection with cyto-kine-mediated inflammatory damage. Alternatively, HHSmight be caused directly by prolonged seizure activity,resulting in increased intracellular calcium, cytotoxicoedema, and eventual neuronal apoptosis. It may be thatthe combination of inflammation and seizures potentiatesneuronal injury. It has been proposed that HHS couldbe considered part of a spectrum of inflammatory medi-ated encephalopathy and status epilepticus syndromes,including fever induced refractory epileptic encephalopa-thy in school-aged children (FIRES) and new-onsetrefractory status epilepticus (NORSE), with the differ-

ences in clinical expression related to the stage of brainmaturation.5

IMPLICATIONS FOR CLINICAL PRACTICE ANDFUTURE RESEARCHThe differential diagnosis of hemiparesis following a febrileseizure in young children is wide, including seizure with po-stictal paralysis (Todd’s paresis), ischaemic or haemorrhagicstroke, intracranial neoplasm, encephalitis, cerebral abscess,acute disseminated encephalomyelitis, and metabolic en-cephalopathies. Recognition of the distinctive MRI appear-ances of HHS, including basal ganglia and hippocampalinvolvement, may help to make an early diagnosis and togive an accurate prognosis. It remains to be seen whetherearly MRI changes are of value in predicting the develop-ment of subsequent epilepsy (HHE syndrome). The distinc-tive imaging appearances of HHS suggest a uniquepathophysiological mechanism; advanced MRI, includingdiffusion and perfusion imaging, may be helpful in elucidat-ing this mechanism.

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1. Gastaut H, Poirier F, Payan H, Salamon G, Toga M,

Vigouroux M. H.H.E. syndrome: hemiconvulsions,

hemiplegia, epilepsy. Epilepsia 1960; 1: 418–47.

2. Freeman JL, Coleman LT, Smith LJ, Shield LK. Hem-

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R, Laverda AM. Hemiconvulsion-hemiplegia-epilepsy

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sion-hemiplegia syndrome revisited: longitudinal find-

ings in 10 children. Dev Med Child Neurol 2013; 55:

1150–8.

5. Nabbout R, Vezzani A, Dulac O, Chiron C. Acute

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lepticus. Lancet Neurol 2011; 10: 99–108.

1074 Developmental Medicine & Child Neurology 2013, 55: 1069–1074