Hemispherotomy in an infant with hemimegalencephaly.

Hemimegalencephaly (HME) is a rare hamartomatous congenital malformation of the brain. The epilepsy pattern in HME can be partial seizures or may present as spasms as in epileptic encephalopathy. Epilepsy associated with HME is usually resistant to antiepileptic drugs and requires surgical intervention. Hemispheric disconnection has been reported to be efficient in seizure control and prevents further cognitive injury and developmental delay. We report a case of HME, who underwent a two-stage hemispherotomy due to complications in the first surgery. She had more than 90% reduction of seizures with good developmental outcome on follow-up. Thus, despite risks of the procedure, early surgery should be preferred in infants with HME.

Introduction

Hemimegalencephaly (HME) is a rare congenital malformation of the brain characterized by overgrowth of one hemisphere.[1] Its prevalence ranges from 1 to 3 cases/1000 epileptic children and 1–14% among those with cortical developmental abnormalities.[234] It has variable presentation ranging from partial seizures to epileptic encephalopathy, hemideficits, and mental retardation. Epilepsy associated with HME is usually resistant to antiepileptic drugs and requires surgical intervention.[14] Here we present a case of HME who underwent a two-stage hemispherotomy due to complications in the first surgery.

Case Report and Summary

A 24-month-old girl (DG) was referred to our center at 2 months of age for refractory seizures. She was born at full term with a normal perinatal history. Her seizure onset was at 1½ months of age. Initially, she had multiple episodes of multifocal clonic seizures followed by left partial seizures. By 4 months of age, she developed infantile spasms. She was tried on multiple antiepileptic drugs like phenobarbitone, phenytoin, clonazepam, levetiracetam, and topiramate without any relief. By first 6 months of age, she had not achieved any milestones.

Her first magnetic resonance imaging (MRI) (at 2 months of age) showed widespread cortical dysplasia in the right hemisphere; however myelination was incomplete [Figure 1a]. Follow-up scans were advised which revealed right-sided HME [Figure 1b and c]. Initial electroencephalogram (EEG) depicted gross asymmetry between the two hemispheres with occasional epileptiform discharges from right frontotemporal region with right-sided theta delta bursts [Figure 1d]

Figure 1

(a) Magnetic resonance imaging (MRI) brain (T1-weighted image) at 2 months of age showing widespread cortical dysplasia in the right hemisphere. (b and c) MRI brain (T2-weighted and T1-weighted images) at 9 months of age showing right sided hemimegalencephaly. (d) Initial electroencephalogram showing gross asymmetry between two hemispheres with occasional epileptiform discharges from right frontotemporal region with right-sided theta delta bursts

In view of resistant epilepsy, due to a structural etiology, a decision of hemispherotomy was taken. She underwent surgery (right temporal lobectomy, callosotomy followed by deafferentation) at 9 months of age. However, during the surgery, she developed complication in the form of intraventricular hemorrhage (IVH). Complete functional hemispherotomy was abandoned in view of hemodynamic instability. An intraventricular drain was inserted. Postoperatively, her computed tomography brain showed IVH [Figure 2a]. In the immediate postoperative period, she was hemodynamically stable and did not have any seizures. MRI brain study done 6 weeks postoperatively showed incomplete disconnection between the two hemispheres [Figure 2b]. Her EEG 6 weeks postoperatively showed gross asymmetry without any epileptiform discharges [Figure 2c]. By this time, her spasms had stopped and she started attaining milestones but her left side paucity of movements was marked. Eventually, she achieved head holding and started socializing. Her seizure frequency decreased over next 6 months to occasional partial seizures.

Figure 2

(a) Computed tomography brain (axial view) after first surgery showing intraventricular hemorrhage (b) Magnetic resonance imaging brain (T1-weighted images) after first surgery showing incomplete disconnection between the two hemispheres. (c) Electroencephalogram (post first surgery) showing asymmetry between two hemispheres without any epileptiform discharges

However, after 6 months postoperatively, spasms recurred with further regression of milestones. EEG showed unihemispheric abnormalities [Figure 3]. She was given a trial of vigabatrin, but seizure control was less than 50%. Frequency of partial seizures also increased to multiple times per day. In view of epileptic encephalopathy, it was decided to complete the functional hemispherotomy. A second surgery was done with complete callosotomy at 18 months of age. She withstood the procedure well. Postsurgery her spasms stopped but occasional partial seizures continued. Repeat neuroimaging (MRI brain) showed complete disconnection between the two hemispheres [Figure 4]. EEG revealed multiple subclinical seizures from right hemisphere. Post second surgery there was more than 75% seizure reduction; there were no spasms, but subclinical seizures still persisted along with left-sided hemiparesis.

Figure 3

Electroencephalogram at 1-year of age showing right-sided unihemispheric abnormalities and subclinical seizure discharges

Figure 4

Magnetic resonance imaging brain (T1- and T2-weighted images) post second surgery showing complete disconnection between the two hemispheres and other postoperative changes

Now with 15 months follow-up after second surgery, she has more than 90% reduction of seizures with complete stoppage of spasms and has no epileptic encephalopathy. The child's development is steadily progressing. However, EEG still shows occasional subclinical seizure discharges.

Discussion

The typical clinical presentation of HME comprises psychomotor retardation, contralateral motor deficit, and intractable epilepsy.[14] The severity of this triad varies among patients ranging from mild to severe.[45] The cerebral cortex of the megalencephalic hemisphere is generally abnormal. The histologic findings seen in the brain tissue include abnormal gyration (lissencephaly, pachygyria, or polymicrogyria), disturbed cortical organization, loss of laminar architecture, poor gray-white matter differentiation, scattered or nodular neuronal heterotopia, abnormal glial cells (balloon cells), giant neurons, mild or severe lack of myelination, and Rosenthal fibers.[6]

Epilepsy is the most frequent and severe neurologic manifestation in patients with HME.[17] The epilepsy pattern in HME can be partial seizures or may present as spasms as in epileptic encephalopathy, either Ohtahara syndrome or West syndrome. Mental retardation and contralateral hemiparesis are generally associated with early epilepsy which is highly resistant and at times mandates surgery.[17] The functional outcome is dependent on seizure frequency, presence of epileptic encephalopathy, and age of presentation.[14]

Hemispherectomy, originally described as the anatomical removal of one of the hemispheres, had been the treatment of choice in catastrophic epilepsy as in HME. Surgical approach has now evolved to functional hemispherectomy or hemispherotomy, the goal and result remains the same. Hemispheric disconnection (mainly anatomic hemispherectomy, peri insular hemispherectomy, modified lateral hemispherotomy, vertical parasagittal hemispherotomy) have been reported to be efficient in seizure control as well as it prevents further additional cognitive injury and developmental delay.[78910] There is no difference in surgical outcome based on different surgical approaches. Anticipated adverse effects of surgery are worsening of hemiparesis in addition to typical surgical risks like bleeding, infection, and potential for developing hydrocephalus.[49] These surgical risks are present in anatomical hemispherectomy more than hemispherotomy procedures.[4] The most frequent complication in infants is intraoperative bleeding; intraoperative blood loss presents a major challenge due to low weight.[11] In our case, we had to abandon the completion of hemispherotomy in the first surgery due to bleeding and hemodynamic instability.

Potential benefits on cognition and development have increased the urgency to properly evaluate and treat them early with the surgical option. Neural plasticity considerations are often invoked as a rationale for performing early surgery.[1213] Earliest reported HME has been operated at 2 months of age.[14] The age at surgery seems to play a major role; more than 90% reduction in seizure frequency is obtained in three-fourths of the patients operated on before age 3 years.[15] However, the absolute contribution of earliest age at the time of surgery is imprecisely known.[15] In our case, the first surgery was performed at 9 months of age, though an incomplete procedure, the child did show a remarkable reduction of seizures initially with stoppage of spasms and improvement in functional development. There was a resurgence of epileptic encephalopathy within 6 months at which a second surgery (an extension of the first surgery) was contemplated. On follow-up, the child had significant reduction of seizures and a good developmental outcome.

The postsurgery prognosis for HME is not so good as that for focal lesions or other hemispheric abnormalities, either malformative or nonmalformative.[91215] The integrity of the non-HME hemisphere is also considered an important factor in the postsurgery prognosis, but this information is not easy to access.[15] Honda et al. have shown that shorter seizure duration is correlated with greater postoperative developmental quotient in infants having HME with epileptic encephalopathy. Surgery at a very early age in infancy poses its own risks, however delaying surgery may put the infant at risk of epileptic encephalopathy.[14] Despite risks of procedure, early surgery should be preferred given the adverse effects of long term antiepileptics, postoperative functional plasticity, and good developmental outcome.

Conclusion

Structural malformations of the brain are usually associated with resistant epilepsy. Few of these malformations may be candidates for surgery and early surgery has been shown to have a better developmental outcome.