CASE REPORT

Hemimegalencephaly without epilepsy: case report

Greg James & Mano Shanmuganathan & William Harkness

Received: 4 February 2014 /Accepted: 19 February 2014# Springer-Verlag Berlin Heidelberg 2014

Abstract Hemimegalencephaly is a rare sporadic brain mal-formation characterized by enlargement of one cerebral hemi-sphere. The classical clinical triad consists of intractable epi-lepsy, severe psychomotor delay and hemiparesis. In thisreport, we describe a case of a 3-year-old girl, with all theradiological features of severe hemimegalencephaly but witha comparatively benign clinical course. She had nohemiparesis, mild delay and no seizures. An extensive litera-ture review reveals only one previously reported case ofhemimegalencephaly with the absence of seizures, as part ofcase series. This is the first dedicated case report, with clinicaldescription and radiological images, of this entity.

Keywords Hemimegalencephaly . Seizures . Brainmalformation . Epilepsy

Introduction

Hemimegalencephaly is a rare, sporadic, hamartomatous con-genital brain malformation characterized by hypertrophy ofone cerebral hemisphere [1, 2]. It is currently classified as amalformation due to abnormal neuronal and glial proliferation[3], and its pathogenesis and aetiology are obscure [2, 4]. Theclassical clinical triad described is of epilepsy, severe psycho-motor retardation and contralateral hemiparesis [1, 2, 5]. The-se conditions are often severe in nature and, indeed, areassociated with a significant mortality in infancy [2, 6]. Onsetof symptoms commonly occurs in the first week of life [5].The treatment of choice for these patients is often surgicalhemispherectomy, either anatomical or functional [4].

However, there have been isolated reports of milder clinicalmanifestations. In the largest published series, one of 14patients was reported as not having seizures [5]. In addition,a case of a patient with normal cognitive development at age19 has been described. This patient did have seizures, al-though relatively mild and responsive to antiepileptic medi-cation [7]. In this article, we describe a child who presented toour department with macrocephaly only, without seizures andwith mildly delayed neurological development, who has aradiological diagnosis of hemimegalencephaly.

Clinical case

A 3-year-old female patient was referred to our neurosurgicaldepartment as her family physician had noted macrocephalyon routine follow-up.

She had been born at term and in good condition but post-partumwas treated as an inpatient for 2 weeks to establish oralfeeding. She had been noted at birth to have hypertrophy of herleft hemisoma with extensive cutaneous vascular anomalies onthis side of the body and extra digits on both feet. Head circum-ference at birth was 42.5 cm with a normotensive anteriorfontanelle. Shewas reviewed by a number of specialist paediatricphysicians and a diagnosis of cutis marmorata telangiectaticacongenita was made. She had mildly delayed neurological de-velopment: at 3 years of age, she was able to walk, but not run;use a pencil; had a vocabulary of 20 words; was socially inter-active. She favoured her left hand but was able to use both. Shehad no clinical evidence of hemiparesis. She has never had aseizure or seizure-like episode as per 42 months of age.

A neurosurgical opinionwas requested due to her large head.On review in the clinic, a head circumference over the 99th centilewas noted but no signs or symptoms of raised intracranialpressure. When the head circumference was plotted on a growthchart, there had been no crossing of centile lines, therefore

G. James (*) :M. Shanmuganathan :W. HarknessDepartment of Neurosurgery, Great Ormond Street Hospital forChildren, LondonWC1N 3JH, UKe-mail: greg.james@nhs.net

Childs Nerv SystDOI 10.1007/s00381-014-2392-9

consistent with normal growth for this child. The referring teamhad organized an MRI brain, and this was reviewed.

Radiological findings

MRI demonstrated features typical of hemimegalencephaly(Fig. 1). Extensive asymmetrical abnormalities were noted,with the left hemisphere clearly larger in volume than theright. This asymmetry was associated with abnormalities bothof grey and white matter. The left hemisphere demonstratedcortical malformation with “cobblestone” appearance andpolymicrogyria, as well as generalized loss of white matterbulk. There was thickening of the left fornix and straighteningof the left frontal horn associated with asymmetry of theventricular system. Radiological features were all consistentwith hemimegancephaly.

The family and referring team were informed that the childdid not require neurosurgical intervention currently, but thatshe was at risk of developing epilepsy and should be closelyobserved for clinical seizures.

Discussion

Hemimegalencephaly is a rare condition, and there is a lack oflarge series in the literature. In one of the largest and mostcomprehensive reviews, the authors describe 14 cases, examin-ing clinical, radiological and electrophysiological features [5]. Inthis series, the authors report that one patient did not haveseizures. A thorough electronic database search did not revealany further cases of hemimegalencephaly without seizures, mak-ing the current case only the second reported, and the only onedescribed with clinical information and radiological images.

Severe epilepsy is a hallmark of the condition, being pres-ent in all 10 patients described in another large series [2]. Infact, hemimegalencephaly carries a significant mortality riskdue to the severity of the epilepsy [6, 8], as well as associationwith significant psychomotor delay and hemiparesis. Thecurrent case is unusual in only having one of the clinical triad(delay), and this only in mild form.

There have been isolated case reports of less severe mani-festations, including one of a 19-year-old male with normalpsychomotor development [7]. However, this patient did sufferwith epilepsy. These seizures were partial in nature, late onset(started in teens) and well controlled on antiepileptic drugs.

What accounts for the relatively benign clinical course inthe current case? Previous attempts have been made to dividehemimegancephaly cases on the basis of severity. Vigevanoet al., in their series of 14 patients [5], divided them into twogroups: A and B. Group A was characterized by severe,uncontrollable epilepsy with marked hemiparesis and delay(7/7), whilst group B had more mild clinical features withsporadic seizures and a later onset of epileptic attacks. Radio-logical features were less severe in group B, with no patient,for example, having microgyria on their scan.

It may be that the current case represents a “group B”-typechild, who is as yet too young to have had her first seizure.Certainly her clinical phenotype is consistent with the patientsreported in this group. Interestingly, however, her markedcortical malformation including polymicrogyria was consis-tent with the radiological features of the more severe “groupA”. On this basis, she does not appear to fit into either of thesedescribed categories, and it may be that she represents aunique case. In the current case, the brain malformation wasassociated with a hemihypertrophy syndrome (cutismarmorata telangiectatica congenita). It is thought that so-

Fig. 1 MRI appearances of3-year-old girl with milddelay and no seizures. Imagesdemonstrate typical features ofhemimegalencephaly, includingenlarged left hemisphere withstraightening of frontal horn,hypertrophied left fornix,ventricular dysmorphism, whitematter changes and corticalanomalies including“cobblestone” appearance of thegyri and polymicrogyria of the leftfrontal lobe. a coronal FLAIR. b–d axial T1. E–h axial T2

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called syndromic hemimegancephaly does not differ in itsseverity or clinical characteristics from the isolated form [9].

The other possibility is that there is a cohort of “silent”hemimegancephaly, with absent or mild clinical signs butradiological features of the malformation, in the communityand that this was an incidental finding when the child wasbeing investigated for unrelated reasons. As access to MRIscanning becomes ever more widespread, it may be thatfurther similar cases are detected as children have brain imag-ing for various, non-seizure reasons. It is our belief that thisexplanation is less likely, as it seems counterintuitive that thesevere cortical and white matter anomalies that definehemimegalencephaly do not cause clinical sequelae.

References

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3. Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns WB(2001) Classification system for malformations of cortical develop-ment. Neurology 57:2168–2178

4. Di Rocco C, Battaglia D, Pietrini D, Piastra M, Massimi L (2006)Hemimegalencephaly: clinical implications and surgical treatment.Child’s Nerv Syst 22:852–866

5. Vigevano F, Fusco L, Granata T, Fariello G, Di Rocco C, Cusmai R(1996) Hemimegalencephaly: clinical and EEG characteristics. In:Guerrini R, Andermann F, Canapicchi R, Roger J, Zifkin BG,Pfanner P (eds) Dysplasias of cerebral cortex and epilepsy.Lippincott-Raven, Philadelphia, pp 285–294

6. Vigevano F, Bertini E, Boldrini R, Bosman C, Claps D, DiCapua M, Di Rocco C, Rossi GF (1989) Hemimegalencephalyand intractable epilepsy: benefits of hemispherectomy. Epilepsia30:833–843

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9. Sarnat HB (2002) Commentary by series editor. J Child Neurol 17:384

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