Periventricular nodular heterotopia, frontonasal encephalocele, corpus callosal dysgenesis and arachnoid cyst: A constellation of abnormalities in a child with epilepsy.

A 7-year-old male child presented with poorly controlled generalized tonic-clonic seizures. On examination, he was mentally retarded, deaf and had a swelling at the root on the nose. Computed tomography scan done previously revealed a left temporal arachnoid cyst (AC) due to which he was referred for surgery. However, magnetic resonance imaging revealed a constellation of abnormalities - all of which could be responsible for his seizures. The combination of periventricular nodular heterotopias with encepaholcele is rarely described in the literature, and more infrequently so its combination with AC and callosal dysgenesis - the Chudley-Mccullough syndrome. We describe the case and review relevant literature on this subject.

Introduction

Magnetic resonance imaging studies are done in children with epilepsy with the aim of identifying any structural lesions that may be responsible for the same. The aim is both to prognosticate outcomes and guide proper management (either medical or surgical). While imaging may be normal, often multiple abnormalities are seen which may be part of a developmental syndrome. The challenge in these cases is to try to isolate if any one of these is responsible for the epilepsy so that a decision can be taken if surgical treatment of the same will be beneficial.

Case Report

A 7-year-old male child, born at term, of a nonconsanguineous marriage presented with a history of poorly controlled generalized tonic-clonic seizures that started 3 years ago. He had a younger brother aged 4 years who was stated to be normal. A variety of antiepileptic medications had been administered with unsatisfactory results. A computed tomography scan done previously showed a left temporal arachnoid cyst (AC) and the child was referred for considering the possibility of surgery. Interictal electroencephalogram (EEG) showed generalized cerebral dysrhythmia. On examination, the child was found to be mentally retarded. His head circumference was normal. Motor functions were well developed. He was aphasic and had bilateral deafness on clinical examination. He had a soft nonfluctuant swelling at the root of his nose due to which he appeared to have hypertelorism. This swelling, according to his parents, was noticed at 1-year after birth and was slowly increasing in size [Figure 1].

Figure 1

Clinical photograph of the patient showing swelling at the root of and over the bridge of the nose causing apparent hypertelorism

A magnetic resonance imaging (MRI) scan was done that showed left temporal AC with left hemispheric periventricular nodular (PVN) heterotopia that was extending to the frontal horn of the left lateral ventricle. Corpus callosal dysgenesis was also seen along with a frontonasal encephalocele. The cortex on the side of the heterotopia was thin compared with the contralateral side [Figures 2 and 3]. We were not convinced regarding the contribution of the AC in seizure genesis in the presence of PVN and callosal abnormalities. Surgery was offered for the encephalocele only, but the family refused any further investigations and treatment.

Figure 2

Coronal T2-weighted and axial T1-weighted magnetic resonance imaging sections showing heterotopic grey matter seen in the left hemisphere (closed arrows), abutting the ventricular ependyma of the frontal horn. A left temporal arachnoid cyst (open arrow) is also seen

Figure 3

Sagittal T1-weighted magnetic resonance imaging section showing frontonasal encephalocele protruding outwards through a defect in the basal part of frontal bone and extending inferiorly over the nasal bone. Corpus callosal dysgenesis is also seen

Discussion

Grey matter heterotopias are congenital errors of neuronal migration that normally takes place sequentially outwards from the subependymal layer to the cerebral cortex.[1] They are of three types – band, focal subcortical and subependymal or periventricular.[2] In the latter, clumps of “normal looking” (on MRI) islands of grey matter lie within the white matter. They lie near the ventricle and occasionally may project below the ependymal lining and are the most common variant of heterotopias.[1] Various genetic anomalies have been found in these patients, but males with X-linked disease have been noted to have other associated developmental disorders too[2] and this was found in our patient as well though no genetic studies could be done.

There are occasional reports of the association between heterotopia and encephalocele in literature. Roelens et al.[3] describe two series – the first of six patients treated for posterior encephalocele in whom heterotopias were found in 3 on MRI and a second series of 8 autopsy cases of encephalocele in which heterotopias were found in 4- and state that the combined occurrence of the two “may not be accidental.” Balaji et al.[4] have reported a 6-year-old girl with frontonasal encephalocele and subependymal nodular heterotopias. Rojas et al.[5] have also described a case of anterior encephalocele in a 15-year-old girl presenting with epilepsy who was found to have subependymal nodular heterotopia with partial agenesis of corpus callosum. Martínez-Lage et al.[6] had found two patients with heterotopias in 46 children treated for cephalocele (both anterior and posterior) and stated that one of the predictors of good outcome was lack of disorders of neuronal migration.

An association between heterotopia and AC with sensorineural deafness has also been reported in the Chudley-Mccullough syndrome.[7] We found only one such case (Nadkarni et al.[8]) reported from India. The disease is supposed to be due to a mutation in the G-protein signaling modulator 2 gene on chromosome 13. Most but not all cases reported have had hydrocephalus usually due to block at the foramen of Munro. None of them had an encephalocele. Our patient did not have hydrocephalus, but did have heterotopias, callosal dysgenesis, sensorineural deafness and an AC as well as an anterior encephalocele. Whether this was a variant of the same syndrome cannot be commented on as genetic studies could not be done.

Arachnoid cyst's of the temporal fossa are associated with partial agenesis of the temporal lobe. Whether the latter is responsible for the cyst formation or is a consequence of compression by the cyst is a matter of debate. Epilepsy is often found in patients with AC's and vice versa. Arroyo and Santamaria[9] examining the relationship between AC's and seizure foci concluded that AC's are an incidental finding in epilepsy and “do not necessarily reflect the location of the seizure focus.” In a study of eight patients with AC's and epilepsy, Yalçin et al.[10] found that EEG abnormalities corresponded to cyst location in only one patient. Analyzing the association between intracranial AC's and seizures, Murthy[11] has suggested that in presence of identifiable epileptogenic factors AC's may be incidental whereas in cases where no other cause can be found the association between AC's and epilepsy is more likely. As our patient had PVN seen on imaging, we did not consider that AC was causal in his seizures and did not proceed with surgery for the same.

To conclude, all patients with seizures and AC's must be meticulously searched for other structural abnormalities that may be present as well as undergo a detailed workup before proceeding on any surgery. Secondly, patients with encephaloceles must also be worked up for underlying structural abnormalities, like heterotopias, in the brain. Faulty neural tube closure (resulting in encephalocele) may affect the subsequent process of neuronal migration, and the combination of these may not be just incidental. Finally, a better understanding of the constellation of abnormalities will help to identify children with particular syndromes and aid in counseling the parents about prognosis and risks of subsequent pregnancies.