Ohtahara syndrome associated with hemimegalencephaly and intracranial lipoma.

Hemimegalencephaly is a disorder of cortical malformation and is associated with various disorders including various neurocutaneous syndromes and many seizure types. We present a case of hemimegalencephaly associated with Ohtahara syndrome and intracranial and facial lipoma.

Introduction

Hemimegalencephaly is a rare congenital disorder of cortical formation with hamartomatous overgrowth of all or a part of a cerebral hemisphere. This results from either increased proliferation or decreased apoptosis (or both) of developing neurons.[1]

Early infantile epileptic encephalopathy, or Ohtahara syndrome, is one of the most severe forms of age-related epileptic encephalopathies, characterized by the onset of tonic spasms within the first 3 months of life. The characteristic electroencephalogram (EEG) displays a burst suppression pattern. Structural abnormalities of the brain are often associated. We present a case of hemimegalencephaly associated with facial and intracranial lipoma presenting as Ohtahara syndrome.

Case Report

A 3-month-old child of nonconsanguineous marriage, presented with a history of tonic neck flexor spasms since 20 days, in clusters, 3–4 clusters/day and 5–6 spasms/cluster. She also had a facial mass on the left side since birth, which is soft, nonprogressive in size and is restricted to the left side of the face. She was born at term gestation with birth weight of 2.5 kg, with no adverse events. Child had not attained any developmental milestones, and was not recognizing mother, had no neck control, but was able to unfist her hands spontaneously.

On examination, she weighed 4.5 kg, and head circumference was 38 cm. A mass was present on the left side of her face. The mass was about 7 cm in diameter, soft in consistency, with smooth borders. The mass was easily movable over the underlying surface [Figure 1]. Left ear was also set lower than the right and larger in size than the right ear. On neurological exam, tone was increased bilaterally right more than left and power on the right side was 3/5 (MRC grade) and 4/5 on the left side.

Figure 1

Clinical photograph of child showing soft tissue swelling on left side of the check

On investigation, complete blood count, serum electrolytes, and serum calcium were within normal limits. EEG findings were suggestive of burst suppression pattern [Figure 2]. Magnetic resonance imaging (MRI) showed a hyper intense lesion in the subcutaneous plane on the left side of face suggestive of a lipoma on axial T1-weighted imaging (T1-WI) [Figure 3a]. Axial T1-WI also demonstrated a hyper intense lesion in the ambient cistern on the right side suggestive of lipoma [Figure 3b]. Axial T2-WI demonstrated left-sided hemimegalencephaly with an enlarged hemisphere and midline shift of the left occipital lobe [Figure 3c]. Axial fluid-attenuated inversion recovery image showed asymmetric cerebellum with abnormal folia [Figure 4a]. Computed tomography brain showed left hemimegalencapahly and intracranial calcification in the right ambient cistern demonstrating a calcified lipoma [Figure 4b].

Figure 2

Electroencephalogram showing multifocal bursts of spikes, sharp waves, and poly-spikes followed by suppression lasting for 3–4 s suggestive of burst suppression pattern

Figure 3

(a) Axial T1-weighted imaging (T1-WI) demonstrating a hyperintense lesion in the subcutaneous plane on the left side of face suggestive of a lipoma. (b) Axial T1-WI demonstrating a hyperintense lesion in the ambient cistern on the right side suggestive of lipoma. (c) Axial T2-WI demonstrating left sided hemimegalencephaly with an enlarged hemisphere and midline shift of the left occipital lobe

Figure 4

(a) Axial fluid-attenuated inversion recovery image showing asymmetric cerebellum with abnormal folia. (b) Computed tomography scan image demonstrating a calcified lipoma in the ambient cistern on right side

Child was treated with injection adrenocorticotropic hormone 24 IU daily for 2 weeks and valproate with partial control of spasms.

Discussion

Partial motor, or partial complex seizures are the most frequent types of epilepsy in hemimegalencephaly and are associated with infantile spasms in 50% of patients. Developmental delay is often early and severe, though variations are often present.[2] Our child had global developmental delay. Anomalies of cortical development including polymicrogyria, pachygyria, and gray-matter heterotopias are always seen in the affected portions of the hemisphere, but can be seen in the “unaffected” hemisphere as well.[2]

Ohtahara syndrome is a severe epileptic syndrome that is characterized by early onset (<3 months of age) tonic/epileptic spasms, either in clusters or sporadic, with burst suppression pattern in both awake and sleep studies. Epileptic spasms occur in sleep as well as in awake state. Daily seizure frequency is high, ranging from 10 to 300 single spasms or 10–20 clusters of spasms. Seizures are partial in one-third to one-half cases. Affected patients show marked developmental and neurological abnormalities after birth, which progressively deteriorates with the course of the disease.[3] Our case presented with tonic infantile spasm in the 3rd month of life and EEG showed burst suppression pattern.

Hemimegalencephaly is associated with Legius syndrome and many other neurocutaneous syndromes such as Proteus syndrome, Incontinentia Pigmenti, and Epidermal Nevus Syndrome. Legius syndrome is a neurofibromatosis (NF) like syndrome, with café-au-lait macules, lipomas, axillary freckling, hemimegalencephaly, and macrocephaly. The child was evaluated clinically and investigated for the same, but no evidence for the diagnosis of Legius syndrome and other syndromes could be found. Legius syndrome is caused by mutations in SPRED1 gene and has many overlapping features with NF1, but has milder clinical manifestations and the neurofibromas and cortical dysplasia characteristic on NF1 do not develop in Legius syndrome.[4]

Ohtahara syndrome is caused by mutations in various genes including ARX, CDKL5, SLC25A22, STXBP1,[5] KCNQ2,[6] and likely others; and various metabolic disorders and structural malformations in the brain. Metabolic workup is normal in our child. In our case, MRI of brain showed hemimegalencephaly; hence mutation analyses for various genes were deferred.

Conclusion

Underlying brain malformations should be considered when evaluating cause for Ohtahara syndrome with lipoma. Extensive metabolic and genetic tests can be avoided.