Anterior striatum with dysmorphic neurons associated with the epileptogenesis of focal cortical dysplasia
Article Outline
Abstract
The epileptogenesis of the striatum is unknown. We describe the case of a 12-year-old girl with intractable epilepsy who was treated by surgical interventions. Magnetic resonance imaging (MRI) showed ambiguous corticomedullary boundary in the left frontal lobe, and magnetoencephalography (MEG) revealed spike dipoles in the vicinity of the left ventral striatum. The epileptic seizures disappeared after partial resection of the frontal lobe, but recurred within 2 months and remained intractable. Neuropathological examination confirmed the presence of focal cortical dysplasia in the resected brain tissue. Ictal single photon emission computed tomography at this period displayed hyperperfusion of the left anterior striatum. At the second surgery, intraoperative electrocorticography exhibited spike discharges from the anterior striatum. After the removal of this structure and adjacent brain tissues, the patient remains seizure-free for 33 months, without any neurological deficits. Histopathological examination of the resected tissue revealed a large number of dysmorphic neurons distributed widely in the cerebral cortex, subcortical white matter, striatum, and insular cortex. These findings suggest that microscopic dysplasia of basal ganglia can accompany certain cases of focal cortical malformations, and may play a critical role in the epileptogenesis through their interaction with cortical structures.
Keywords: Dysmorphic neuron, Striatum, Epilepsy, Malformation, Cortical dysplasia
1. Introduction
Recently, it is suggested that the basal ganglia, such as striatum, participate in propagation pathway, executing some aspects of the ictal process, or control of epileptic activity as a homeostatic factor.1 Epileptogenesis of striatum, however, is unknown still in nowadays.
We here report a surgical case of the removal of frontal lobe including anterior part of striatum based on ictal hyperperfusion and electorical activity. Dysmorphic neurons were confirmed not only in frontal lobe but also in striatum pathologically.
2. Case
The patient, a Japanese girl, experienced generalized tonic seizures for the first time at the age of 11 months, which persisted with a frequency of several times per year despite medical treatment. At the age of 4 years, status epilepticus with asymmetric tonic seizures first appeared, and recurred once per 2 years. Delayed psychomotor development was noted thereafter, with an intelligent quotient of 43 at 12 years of age. Intractable daily seizures persisted since the age of 10. At the age of 12, the patient was admitted to our hospital.
At this period, the patient showed a seizure type of hypermotor behaviors followed by tonic seizures. Brain magnetic resonance imaging (MRI) revealed indistinct corticomedullary boundary in the left orbitofrontal cortex (Fig. 1A–C). Interictal electroencephalogram (EEG) showed intermittent theta waves at the left frontopolar area. Interictal 123I-iomazenil single photon emission CT (SPECT) and fluorodeoxyglucose positron emission tomography (FDG PET) demonstrated hypoperfusion and hypometabolism at her left orbitofrontal cortex, respectively. Magnetoencephalography (MEG) showed a cluster of spike dipoles at the left frontal deep white matter adjacent to the anterior striatum (Fig. 1D–F). Subdural electrode grids were implanted over the left frontal region, which detected the seizure onset area at the left fronto-orbital surface. Based on these findings, resection of the left frontal lobe, including left fronto-orbital surface, was carried out. Neuropathological examination of the resected tissue confirmed the diagnosis of focal cortical dysplasia.
Fig. 1.
Neuroimaging of the patient. Magnetic resonance imaging (MRI) (A–C) showed unclearness of corticomedullary border in the left frontal lobe. Magnetoencephalography (MEG) (D–F) revealed a cluster of spike dipoles at the deep white matter of the left frontal lobe and the anterior striatum. MEG was measured using a 204-channel MEG system (VcctorView; Neuromag Co., Helsinki, Finland). Dipole sources with a goodness of fit greater than 80% (circles) were accepted and overlaid on the MRI results. 99mTc-ethyl cysteinate dimer single photon emission computed tomography (SPECT) with superimposition on the magnetic resonance imaging (MRI) (G–I) after the first operation demonstrated ictal hyperperfusion at the left deep frontal lobe and the nucleus accumbens in red with Z scores greater than 2. MRI after the second operation (J–L) illustrated that the left deep frontal lobe and a part of the nucleus accumbens and the head of the caudate nucleus had been removed. A, D, G, and J: axial view; B, E, H, and K: coronal view; C, F, I, and L: sagittal view.
Seizures disappeared for 2 months after resection surgery, but re-emerged and became daily again. Ictal SPECT showed significant hyperperfusion at the anterior striatum, including the nucleus accumbens (Fig. 1G–I). At 13 years of age she received the second resection surgery 17 months later from the first surgery. Two depth electrodes (UZN D4-06-054-151-101-A, Unique Medical Co., Komae, Tokyo, Japan) were implanted stereotactically into the anterior striatum. An electrode was into the anterior striatum corresponding to the hyperperfusion area, and another was into the caudate head. From the depth electrode into the nucleus accumbens, independent spikes were captured (Fig. 2). Extended resection of the residual tissue of the left frontal lobe, anterior insular cortex, and striatum: caudate head and nucleus accumbens, was performed (Fig. 1J–L). Histopathological examination of the specimen revealed a large number of dysmorphic neurons distributed widely in the cerebral cortex, subcortical white matter, striatum, and insular cortex (Fig. 3). The cortex showed marked cytoarchitectural abnormalities. The caudate head and nucleus accumbens were identified by the relative orientation to the ventricle and subventricular zone, and the presence of striatal axon bundles (Fig. 3A), where several neurons demonstrated large, dysmorphic features (Fig. 3B and C). They had coarse Nissl substance and prominent nucleoli. Similar, but much larger, dysmorphic neurons were also observed in the insular cortex (Fig. 3D). No balloon cells were seen in anywhere of the specimen. The patient was discharged without any neurological deficit, and has been seizure-free for 33 months postoperatively.
Fig. 2.
Intraoperative electroencephalography from the depth electrode inserted stereotactically at the second operation revealed spike discharges from the left anterior striatum. Tentative target of the nucleus accumbens was between A1 and A2 of grids. The interval of each electrodes of the inserted part was 5
mm.
Fig. 3.
Light micrographs of surgical specimen taken at the second operation. (A) Low-power magnification of the area close to the ventricle (ven) demonstrates orientation of the subventricular zone (SVZ) and the anterior caudate head (ch). The ependymal cell lining is indicated by arrowheads. (B and C) Dysmorphic neurons in the caudate head (B) and nucleus accumbens (C). They are scattered between the axon bundles (p: pencil fibers) in the striatum, or closely packed. (D) Dysmorphic neurons in the insular cortex. Klüver-Barrera stain. Bar
=370μm for A, and 40μm for B–D.
3. Discussion
Initial, preoperative assessment of the present patient showed dissociated findings suggestive for the epileptogenesis either in the orbito-frontal cortex or in the deep frontal area in the vicinity of ventral striatum. According to the textbook of neurosurgery,2 it was emphasized that a frontal lobectomy should be carried out in a wedge-like fashion to avoid the basal ganglia and thalamus. In contrast to these assumptions that the activation of basal ganglia is dependent of the epileptic activity of the dysgenetic cortex, the findings of the present patient provided some evidence that the dysgenetic striatum itself may participate in the epileptogenesis in certain cases.
Dysmorphic neurons were observed in the surgical specimen from the anterior striatum of the present patient. To our knowledge, there are no previous reports histopathologically demonstrating the existence of dysmorphic neurons pathologically in a striatum of an epilepsy patient. In striatal development, three modes of neuronal migration are involved: radial migration of striatal projection neurons, tangential migration of striatal interneurons, and inward migration of preplate neurons.3 Striatal dysplasia may occur during striatal development as a consequence of erroneous migration, maturation, and/or cell death during ontogenesis and plays a part of epileptogenesis like development of cortical dysplasia.4 We believe that dysmorphic neurons are as the result of neuronal maldevelopment of the striatum.
Intraoperative EEG of the anterior striatum in the present case showed spike discharge. This finding may suggest the possibility of electrical activity from the dysgenetic striatum as epileptogenesis. A previous study5 reported the abnormal electrophysiological properties of the cytomegalic neurons in the dysplastic neocortical samples from the pediatric patients. It was observed with patch clamp recordings that these cells had generated large Ca2+ currents and influx when depolarized under the conditions that reduced the contribution of K+ conductance. Vergnes et al.6 reported that smaller amplitude of spontaneous spike and wave discharges were recorded in the striatum in rats with epilepsy. Striatal kindling in rats generated seizures by genuine kindling with the reasons as followed; (1) seizures appeared only after multiple afterdischarges had been triggered, (2) the intensity of the behavioral seizures and the afterdischarge increased with repeated stimulations, and (3) the increased susceptibility to seizures persisted over a rest period without stimulation.7 These reports provide grounds for our proposal that dysplastic neurons of the striatum in the present case generate epileptogenic electrical activity.
After the removal of anterior striatum and frontal lobe, refractory epilepsy had cured with seizure freedom. There are very few but valuable previous reports to show clinical aspects of striatal epileptogenesity. It was believed that tonic spasms in one or two extremities are due to subcortical lesions in such as subthalamic regions and the corpus striatum whereas the exact pathological confirmation is not obtained. These epileptic attacks have been described by the term ‘tonic subcortical epilepsy’.8 An old previous article reported a patient of tuberous sclerosis and epilepsy treated by stereotactic electrolytic lesions, which had cured an epileptic patient with seizure freedom.9 In functional hemispherectomy cases,10 removing most of the thalamus, basal ganglia, caudate nucleus, and associated deep hemispherical structures seems important because they were the areas often implicated in recurrent seizures due to reoperations. Sasaki et al.11 showed a case of an 8-year-old girl of intractable epilepsy due to cortical dysplasia. She had suffered bilateral striatal necrosis and transient seizure freedom for 6 months. The authors thought that the striatum might be involved in the propagation pathway for epileptic seizure activity, but did not mention the possibility of striatal epileptogenesity. There are other previous articles of epilepsy cases associated with striatal lesions such as a tumor.12 These findings may indicate that the striatum of these cases had epileptogenesity.
Acknowledgments
We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Disclosure of conflicts of interest: None of the authors has any conflict of interest to disclosure.
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PII: S1059-1311(10)00032-4
doi:10.1016/j.seizure.2010.02.003
© 2010 British Epilepsy Association. Published by Elsevier Inc. All rights reserved.
