Pathology-Based Approach to Seizure Outcome After Surgery for Pharmacoresistant Medial Temporal Lobe Epilepsy.

BACKGROUND: Hippocampal sclerosis (HS) is the most common cause of drug-resistant medial temporal lobe epilepsy (MTLE). Structural abnormalities such as HS, granule cell pathology (GCP), and focal cortical dysplasia (FCD) have been classified histopathologically, possibly allowing a more accurate assessment of prognostic seizure and neuropsychologic outcomes. We correlated seizure outcome with comprehensive temporal lobe pathologic findings, identified according to the most recent classification systems of HS, GCP, and FCD. METHODS: All the 83 patients who underwent anterior temporal lobectomy (ATL) for drug-resistant MTLE and with a proven diagnosis of HS between April 2001 and May 2014 were collected. Patients were divided in 2 main groups: 1) isolated HS with/without GCP (HS +/- GCP); and 2) HS associated with FCD with/without GCP (HS+FCD +/- GCP). Patients were followed up at least 1 year, and seizure outcome was reported in accordance with Engel classification. RESULTS: Group I: HS +/- GCP: Statistical analysis confirmed a better outcome in HS + GCP patients than in HS-no GCP (P < 0.05). Moreover, a better outcome for the patients affected by GCP type I was observed (P < 0.05). Group II: HS+FCD +/- GCP: Patients with HS variant type I presented a better seizure outcome than the patients with HS type II (Engel class IA HS type I vs. type II: 69% vs. 40%). CONCLUSIONS: A pathology-based approach to epilepsy surgery might improve the interpretation of the results, could predict which cases will enjoy a better seizure outcome, and could help to the comprehension of the causes of failures.

BRAF V600E mutation in neocortical posterior temporal epileptogenic gangliogliomas.

The aim of this study was to verify the presence of BRAF mutations in a series of six patients affected by drug-resistant focal epilepsy associated with neocortical posterior temporal gangliogliomas (GG) who were subjected to lesionectomy between June 2008 and November 2013. GG are an increasingly recognized cause of epilepsy and represent the most common tumor in young patients undergoing surgery for intractable focal epilepsy. BRAF mutations have been identified in up to 50% of GG. Interestingly, these six patients shared a specific anatomical posterior temporal site. In all patients, histological examination confirmed the diagnosis of GG, and two were also associated with a focal cortical dysplasia (FCD) type IIa. BRAF mutations were found in four out of six GG (66.6%). Furthermore, dysplastic tissue of Patient 2 showed a concomitant BRAF V600E mutation. All patients but one (83.3%) achieved Engel Class Ia seizure control. The patient carrying a concomitant BRAF mutation in GG and FCD fell into Engel Class II. Further analyses will be required in order to better understand the meaning of BRAF mutations in epilepsy-associated tumors and FCD and their possible role as a prognostic seizure outcome and tumor behavior marker.

Focal cortical dysplasias in temporal lobe epilepsy surgery: Challenge in defining unusual variants according to the last ILAE classification.

OBJECTIVE: Focal cortical dysplasias (FCDs) represent a common architectural cortical disorder underlying pharmacoresistant focal epilepsy. The recent ILAE classification defines different types of FCDs based on their histopathological features, MRI imaging, and presumed pathogenesis; however, their clinical features and their prognostic significance are still incompletely defined. In addition, the combination of different histopathological abnormalities can represent "unusual" subtypes that can be difficult to classify. The aim of our study was to analyze the incidence and the significance of these "unusual" subtypes of FCDs in drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: We retrospectively analyzed 133 patients consecutively submitted to tailored anteromesial temporal lobe resection for pharmacoresistant MTLE. Seizure onset, seizure duration, age at surgery, and postoperative seizure outcome were evaluated in relation to the different neuropathological groups defined according to the new ILAE classification. RESULTS: Focal cortical dysplasias were found in 80 out of 133 patients. Six patients were affected by isolated FCD type I, 12 patients by FCD type II, and 44 patients by FCD type III. Furthermore, we found 18 "atypical" cases (20.5% of all FCD cases and 26.6% of FCDs associated with a principal lesion): 10 cases of associated FCD type II-hippocampal sclerosis (HS) and 8 cases associated with FCD II-epilepsy-associated tumors (EATs). CONCLUSION: Our results indicate that "unusual" subtypes of FCDs, in particular associated FCD type II, are not uncommon findings, suggesting that they deserve a classification recognition. Similarities in seizure outcome and immunohistochemical and molecular evidences, shared by FCD type II+EATs and EATs, suggest a common pathogenic link. The choice to create a specific unifying class or, on the contrary, to also include "associated FCD type II" in the definition of the new unifying class FCD type III should be further discussed.

Rud syndrome with focal cortical dysplasia: a case report.

We report a female patient with ichthyosis, epilepsy, mental retardation, hypergonadotrophic hypogonadism, polyneuropathy, and cranial dysmorphisms. This clinical picture may satisfy the main diagnostic criteria that characterize Rud syndrome (RS), a rare neurocutaneous disease. The patient underwent extensive clinical evaluation, neurophysiological studies (wakefulness and sleep EEG, EMG), dermatological and endocrinological evaluation and neuroimaging study (3 Tesla brain MRI). Interestingly, brain MRI unveiled a malformation of cortical development, never reported previously in RS. Although seizure semiology and EEG features could not provide clear cut information suggesting a focal onset, the role of this MRI finding in the genesis of the epileptic seizures cannot be ruled out. The finding of a focal cortical dysplasia in RS might be related to genetic abnormalities affecting the development of both epidermis and neural structures with the same embryological origin.

p-ANCA pachymeningitis presenting with isolated "optic neuropathy".

Isolated bilateral optic neuropathy is an exceedingly rare presentation of perinuclear-antineutrophil cytoplasmic autoantibody (p-ANCA) vasculitis. We report one such case with MRI documentation of a compressive mechanism mediated by pachymeningitis. A 69-year-old woman had a 6-month history of progressive visual failure caused by bilateral optic neuropathy. Cranial MRI showed diffuse contrast enhancement of the dura mater extending to the perioptic sheaths bilaterally with encasement of the optic nerves. Extensive laboratory study showed increased levels of p-ANCA titres and autoimmune markers. Corticosteroid treatment improved both visual acuity and the neuroradiological signs of active pachymeningitis. In conclusion, our case demonstrates that bilateral optic neuropathy may be the presenting symptom of p-ANCA-associated pachymeningitis, whose causative role may be demonstrated by MRI.