Nodular heterotopia: A neuropathological study of 24 patients undergoing surgery for drug‐resistant epilepsy

Abstract

Summary Purpose: Despite the availability of detailed electroclinical and imaging data, only a few neuropathological studies of nodular heterotopia have been published. The aim of this study was to describe the neuropathological features of various types of nodular heterotopia obtained from patients undergoing surgery for intractable epilepsy. Methods: Specimens of heterotopic nodules taken from 24 patients were neuropathologically investigated using routine and immunocytochemical procedures, and the data were compared with magnetic resonance imaging (MRI), electroclinical findings, and surgical outcomes. Results: The neuropathological data distinguished two groups. Group 1 (14 patients, 78% in Engel class 1) had similar characteristics regardless of the size, number, or location of the nodules, with both projecting and local circuit neurons in the nodules intermingled with glial cells. Thirteen patients had focal cortical dysplasia. The nodules were identified by MRI in all cases. In group 2 (10 patients, 90% in Engel class 1), all of the nodules were within the temporal lobe and associated with hippocampal sclerosis or gangliogliomas. They were very small (undetected by MRI) and mainly formed by projecting neurons with no evidence of glial cells. All of the patients had cortical dysplasia. Discussion: The distinctive neuropathological features of the nodules in the two groups suggest different etiopathogenetic mechanisms. In group 2, the presence of nodular formations in association with cortical dysplasia and either hippocampal sclerosis or ganglioglioma raises a question concerning so‐called dual pathology in the temporal lobe.

Stereo-EEG-guided radio-frequency thermocoagulations of epileptogenic grey-matter nodular heterotopy

“…In fact, it has been previously demonstrated that the cytoarchitecture of nodules does not differ according to their hemispheric site, or to their depth, either subependimal or subcortical 23. Despite this, RF-THC of the NH was sufficient to provide a favourable result in only four of our five patients.…”

Surgical pathology of epilepsy‐associated non‐neoplastic cerebral lesions: A brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

“…Finally, small “lentiform” heterotopia is usually undetectable by MRI and histologically composed of projecting neurons, which is distinct from the larger nodular heterotopia that is usually detectable by MRI and consists of both projecting and local circuit neurons. 78 Because of the similarity at a glance, it should not be mistaken for a part of the claustrum.…”

Periventricular Nodular Heterotopia: Pathogenesis, Epileptogenesis and Implications in Higher Cerebral Functions

“…Regardless of the etiology, size, number (single or multiple) or topography, heterotopic nodules present similar features and organization, suggesting that there is a final common pathway involved in the formation of the nodules [1,4] . According to some authors, ectopically expressed Reelin is the key factor in this process [21] .…”

“…Heterotopic nodules consist of well-delimited groups of neurons highly differentiated, that emit and receive large sprouts and elaborate dense synaptic terminals, without presenting laminar organization [1,2] . Tractography and functional MRI (fMRI) studies have suggested anatomic and functional connections between heterotopic nodules and overlying cortex, as well as connections between nodules and regions of contralateral cortex, other heterotopic nodules and ipsilateral cortex [23,24] .…”

“…subcortical nodular heterotopias), and range from isolated single nodule to bilateral confluent nodules [1] . This malformation of cortical development can be related to genetic mutations (e.g., FilaminA, ARFGEF2), or extrinsic factors (e.g., irradiation, infection, injury) [2] .…”