Recent technological advances in quantitative histology, with systems such as whole slide imaging with high-throughput, automated analysis (WSA), means that it is now possible to more accurately and efficiently quantify histological stains and immunolabelling, which may aid the clinical diagnosis of a wide range of diseases and be instrumental in the design of personalised treatment plans which may improve patients’ chances of recovery. Consequently, there is a clinical need for the accurate, rapid evaluation of the numerical threshold of ‘excess’ WMN in epilepsy, and to determine any possible relationships between WMN density and epileptogenesis, pharmacoresistance and surgical outcome. Excess density of WMN has also been reported in patients with schizophrenia and autism, suggesting the possibility that the WMN density may be an indicator of neurodevelopmental disorders beyond epilepsy. Findings from previous quantitative studies have been contradictory, due to the small sample size used (<52 cases), and differing counting methods, equipment, regions of analysis, and cell types studied (Additional file 1: Table S1). Despite many previous studies in this field, the oldest dating back to 1984, it is still uncertain whether the density of WMN is increased in patients with epilepsy, what the threshold for the diagnostic confirmation of mMCD II should be, whether the severity of this pathological feature correlates with pre-operative MRI, and represents a clinically relevant, prognostic biomarker, in particular for outcome following epilepsy surgery.
There are presently no other criteria to aid the assessment of mMCD II. This study confirms the potential role of WSA in future quantitative diagnostic histology, especially for the histopathological diagnosis of mMCD.Īccording to the Palmini classification, the observation of ‘excess’ heterotrophic neurons in layer I and the white matter are classified as mild forms of Malformation of Cortical Development (mMCD) type I and II respectively. Using results from WSA manual, we proposed a threshold value for the classification of mMCD II, where 78% of patients now classified with mMCD II were seizure-free at the second post-operatively follow up. We found that, in particular, WSA with user-defined region of interest (manual) was superior in terms of larger sampled size, ease of use, time consumption, and accuracy in region selection and cell recognition compared to other methods. ResultsĪll quantitative systems showed a higher density of white matter neurons in epilepsy cases compared to controls (P = 0.002). Quantitative data from WSA was compared to two other systems, semi-automated quantitation, and the widely accepted method of stereology, to assess the reliability and quality of results from WSA. This study quantified the density of NeuN immunopositive neurons in the white matter of up to 142 epilepsy and control cases using WSA.
Advance in technology leading to the development of whole slide imaging with high-throughput, automated quantitative analysis (WSA) may overcome these differences, and may provide objective, rapid, and reliable quantitation of white matter neurons in epilepsy.
The exact diagnostic criteria for mMCD II are still ill-defined, mainly because findings from previous studies were contradictory due to small sample size, and the use of different stains and quantitative systems. In epilepsy, the diagnosis of mild Malformation of Cortical Development type II (mMCD II) predominantly relies on the histopathological assessment of heterotopic neurons in the white matter.
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