Anterior striatum with dysmorphic neurons associated with the epileptogenesis of focal cortical dysplasia

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.

Basal ganglia dysplasia and mTORopathy: A potential cause of postoperative seizures in focal cortical dysplasia

“…Notably, the basal ganglia imaging changes seemingly correlated with seizure burden at the time. There were histopathological features suggestive of dysplasia, consistent with previous reports of dysmorphic neurons in the basal ganglia of patients with FCD 6,7 . Deep sequencing revealed somatic MTOR mosaicism in both the basal ganglia and overlying cortex.…”

“…Given the mounting evidence for epileptogenicity of dysmorphic neurons in FCD and tuberous sclerosis complex, 16,17 it is conceivable that the dysmorphic neurons in our patient's dysplastic basal ganglia could play an active role in seizure generation. This notion is supported by previous reports of successful seizure control following the resection of basal ganglia structures in patients with FCD who had ongoing seizures despite the removal of cortical lesions 6,7 . Although the underlying genetic basis for these patients is not known, histopathological examination of the resected basal ganglia showed dysmorphic neurons, demonstrating that dysplasia of the basal ganglia can occur in patients with FCD and may contribute to seizure generation 6,7 …”

“…6,7 Although the underlying genetic basis for these patients is not known, histopathological examination of the resected basal ganglia showed dysmorphic neurons, demonstrating that dysplasia of the basal ganglia can occur in patients with FCD and may contribute to seizure generation. 6,7 Somatic MTOR pathogenic variants causing basal ganglia dysplasia may explain why some patients with HME and FCD have postoperative seizures, noting that current approaches to hemispheric malformations such as functional hemispherotomy leave the ipsilateral basal ganglia intact. The dysplastic, ipsilateral basal ganglia that remain following a hemispherotomy might produce seizure manifestations referable to the connected contralateral hemisphere, via minor commissural pathways, potentially leading clinicians to conclude that the patient has a bilateral malformation.…”

Imbalance of interneuron distribution between neocortex and basal ganglia: Consideration of epileptogenesis of focal cortical dysplasia

“…However, it may be based on the imbalance between the excitatory and inhibitory neuronal circuits, which seems to play an important role in the initiation and spread of epileptic seizures [8]. It is of considerable interest that the basal ganglia with dysmorphic neuron of FCD have been associated with epileptogenesis [9]. Recently, we reported that deep structure resection improved seizure control and resulted in no motor deficit after operation [9,10].…”

Branch atheromatous disease has a stronger association with late-onset epileptic seizures than lacunar infarction in Japanese patients

“…12 Several case reports suggest that abnormalities of deep brain structures may play a critical role in epileptogenesis. 13,14 In the present study, we investigated whether subcortical cerebral infarctions (i.e., lacunar infarcts or BAD individually) can increase the prevalence of epileptic seizures in Japanese patients. We also evaluated whether risk factors for seizures and involvement of the basal ganglia or thalamus could be related to seizures.…”