Authors :
Presenting Author: VALERIA MURO, MD – Hospital Britanico Buenos Aires
Monica Mezmezian, MD PhD – Pathology – Institute for Neurological Research FLENI,Bs As, Argentina; Roland Coras, MD – Neuropathology – Department of Neuropathology, University Hospitals Erlangen, Erlangen, Germany; Mariela Petrucci, MD – Hospital Britanico Buenos Aires, Bs As, Argentina; Carlos Rugilo, MD – Neuroimaging – Hospital Britanico Buenos Aires, Bs As, Argentina; Paulina Yañez, MD – Neuroimaging – Institute for Neurological Research FLENI,Bs As, Argentina; Ingmar Blümcke, Dr Prof – Director Institute of Neuropathology University Hospitals Erlangen
Rationale:
Hyaline Astrocytic inclusion (HAI) is a rare histological finding in cases with Drug Resistant Epilepsy(DRE), however, it has recently been recognized in association with Focal Cortical Dysplasia (FCD).
Methods:
A retrospective review of two patients with FCDIIA+HAI by two independent neuroradiologists and histopathologists and a review of literature was conducted.
Results:
Case1: A six year old boy with DRE since five months old, cognitive impairment, and focal motor seizures with frontal semiology. 3TMRI:right fronto-opercular abnormal cortical folding, cortical irregularities, no changes in T2/Flair. PETscan right frontal hypometabolism. Spect negative. Exome panel and chromosomal microarray negative. Right frontal resection at five years old. Outcome: Engel IV-A. Case 2:A six year old boy withDRE since four months old and cognitive impairment, focal motor seizures with right frontal semiology evolving to infantile spasm. Afterwards, he developed focal motor seizures. 3TMRI showed right frontal abnormal cortical folding and thickening. Ictal Spect positive. Exome negative. Frontal partial resection at five years old. Outcome Engel IV A. (Figure 1).
Histopathology: Case 1-2 both evaluators agree on HAI+FCDIIA. Both patients showed cortical lamination, dysmorphic neurons, and brightly eosinophilic inclusions within the astrocytic cytoplasm in the gray matter. Inclusions were negative with PAS/Congo red. By immunohistochemistry, they were positive for S100 and negative for vimentin, GFAP, and neurofilament. Molecular genetic testing not available.
Neuroimaging: First MRI reports were normal. Second MRI was abnormal. Presurgical MRI was evaluated after surgery and were abnormal for both neuroradiologist.
Literature review of HAI and DRE: To date 12 autopsy/biopsy cases with DRE but with limited clinical information and 44 post-surgical specimens of patients with DRE including our cases (Table 2). The etiology was presumed genetic in 6/44. Seizure onset before 24 months-old was observed in all of them.Infantile spasm was reported in 21/44. MRI showed a variety of abnormal sulcus, cortical folding, and polymicrogyria like pattern as well as cortical Gray-WM blurriness. Two patients had normal MRI. Histopathology showed 20 of 44 cases reported only HAI, 4/44 reported HAI +Non Classified Finding and 18/44 with HAI+FCD(4/44 FCDIIA; 7/44FCD IIB; 7/44 FCDI). Only 22% (10/44) of patients achieve seizure freedom. No molecular testing in brain tissue was reported in previous studies. López-Rivera et al 2023 published a collaborative study and 2/474 brain specimens reported FCDIIA+HAI and molecular testing showed a novel association between large chromosome 1q duplications that include AKT3.
Conclusions:
HAI has been described in brain specimens with epilepsy since 1992 and 44 post-surgical patients have DRE with early onset seizures including our cases. We presented 2/6 patients with HAI + FCD IIA and an MRI with polymicrogyria like pattern. The future lay on tissue molecular analysis, and it could help us to identify subgroups and guide us in the decision-making process. HAI it is a histopathological finding that is not quite fully understood however patients who have this clinical picture may be benefit from extensive resection rather limited to the lesion
Funding: No