Ketogenic dietary therapies in epilepsy: recommendations of the Italian League against Epilepsy Dietary Therapy Study Group.

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided.

Risk of hospitalization and death for COVID-19 in persons with epilepsy over a 20-month period: The EpiLink Bologna cohort, Italy.

OBJECTIVE: Data on COVID-19 outcomes in persons with epilepsy (PWE) are scarce and inconclusive. We aimed to study the risk of hospitalization and death for COVID-19 in a large cohort of PWE from March 1, 2020 to October 31, 2021. METHODS: The historical cohort design (EpiLink Bologna) compared adult PWE grouped into people with focal epilepsy (PFE), idiopathic generalized epilepsy (PIGE), and developmental and/or epileptic encephalopathy (PDEE), and a population cohort matched (ratio 1:10) for age, sex, residence, and comorbidity (assessed with the multisource comorbidity score), living in the local health trust of Bologna (approximately 800 000 residents). Clinical data were linked to health administrative data. RESULTS: In both cohorts (EpiLink: n = 1575 subjects, 1128 PFE, 267 PIGE, 148 PDEE, 32 other; controls: n = 15 326 subjects), 52% were females, and the mean age was 50 years (SD = 18). Hospital admissions for COVID-19 in the whole period were 49 (3.1%) in PWE and 225 (1.5%) in controls. The adjusted hazard ratio (aHR) in PWE was 1.9 (95% confidence interval [CI] = 1.4-2.7). The subgroups at higher risk were PFE (aHR = 1.9, 95% CI = 1.3-2.8) and PDEE (aHR = 3.9, 95% CI = 1.7-8.7), whereas PIGE had a risk comparable to the controls (aHR = 1.1, 95% CI = .3-3.5). Stratified analyses of the two main epidemic waves (March-May 2020, October 2020-May 2021) disclosed a higher risk of COVID-19-related hospitalization during the first epidemic wave (March-May 2020; aHR = 3.8, 95% CI = 2.2-6.7). Polytherapy with antiseizure medications contributed to a higher risk of hospital admission. Thirty-day risk of death after hospitalization was 14% in both PWE and controls. SIGNIFICANCE: During the first 20 months since the outbreak of COVID-19 in Bologna, PWE had a doubled risk of COVID-19 hospital admission compared to a matched control population. Conversely, epilepsy did not represent a risk factor for COVID-19-related death.

Ultrasound assisted awake epilepsy surgery for type IIB focal cortical dysplasia in eloquent areas.

Focal cortical dysplasia (FCD) type IIb is a frequent cause of pharmacoresistant epilepsy. However, intraoperative identification of the pathological tissue still remains a challenge despite the use of neuronavigation, particularly when it lies in eloquent areas. We here report a case of intraoperative identification of a right frontal FCD type IIB through ultrasound assisted neuronavigation during awake surgery in a patient with drug-resistant epilepsy. Intraoperative ultrasound may have a role in focal cortical dysplasia localization optimizing its resection. In selected patient submitted to epilepsy surgery the integration of disposable technologies (i.e. brain neuronavigation, fMRI and iUS) with awake surgery could improve FCD identification preventing unacceptable neurological morbidity.

Long-term persistence of NMDAR antibodies after encephalitis with de novo occurrence of demyelinating disorder.

The issue of persistence of NMDAR antibodies after encephalitis is not fully elucidated and their relationship with demyelinating disorders has been suggested. A female patient showed at the age of 18 an acute neurological disorder (with psychiatric symptoms, focal seizures, orofacial dyskinesias and hypoventilation requiring ventilatory support) clinically mimicking anti-NMDAR encephalitis. At that time specific laboratory tests were not available, CSF revealed oligoclonal bands and MRI was negative. The patient had full recovery after first line immunotherapy (i.v. steroids and immunoglobulins). Fifteen years later, at the age of 33, she was hospitalized with subacute right hemiparesis and MRI disclosed multiple T2 hyperintensities in the white matter, one of them in the left midbrain showing contrast enhancement. Serum and CSF NMDAR antibodies were positive while MOG and AQP4 antibodies were negative. Intravenous methylprednisolone led to complete recovery. This case report provides evidence of a long-term persistence of NMDAR antibodies even 15 years after the encephalitis and raises the suspicion of a possible causal relationship between NMDAR antibodies and demyelinating disorders in the form of multiple sclerosis.

Intravenous immunoglobulin therapy in COVID-19-related encephalopathy.

OBJECTIVE: To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. METHODS: We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. RESULTS: Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19-55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1-10 days). No adverse events related to IVIg were observed. CONCLUSIONS: Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.

Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke.

Introduction: Neurological manifestations are emerging as relatively frequent complications of corona virus disease 2019 (COVID-19), including stroke and encephalopathy. Clinical characteristics of the latter are heterogeneous and not yet fully elucidated, while the pathogenesis appears related to neuroinflammation in a subset of patients. Case: A middle-aged man presented with acute language disturbance at the emergency department. Examination revealed expressive aphasia, mild ideomotor slowing, and severe hypocapnic hypoxemia. Multimodal CT assessment and electroencephalogram (EEG) did not reveal any abnormalities. COVID-19 was diagnosed based on chest CT findings and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR (RT-PCR) on nasopharyngeal swab. The following day, neurological symptoms progressed to agitated delirium and respiratory status worsened, requiring admission to the ICU and mechanical ventilation. Brain MRI and cerebrospinal fluid (CSF) studies were unremarkable. RT-PCR for SARS-CoV-2 on CSF was negative. He received supportive treatment and intravenous low-dose steroids. His neurological and respiratory status resolved completely within 2 weeks. Conclusions: We report a patient with reversible COVID-19-related encephalopathy presenting as acute aphasia, mimicking stroke or status epilepticus, eventually evolving into delirium. Although large-vessel stroke is frequently encountered in COVID-19, our case suggests that focal neurological deficits may occur as the earliest feature of encephalopathy. Neurological status reversibility and the absence of abnormalities on brain MRI are consistent with a functional rather than a structural neuronal network impairment.

Autosomal dominant lateral temporal lobe epilepsy associated with a novel reelin mutation.

Reelin mutations are responsible for a minority of families with autosomal dominant lateral temporal lobe epilepsy. Here, we report a novel nuclear family with distinct clinical and neuroradiological findings. We studied the proband and her mother by means of EEG, video-EEG, 3T MRI, FDG-PET and genetic testing. Both patients had a focal drug-resistant epilepsy with onset at the age of 16 and focal seizures with typical auditory features combined with fear, followed by loss of contact or evolving to bilateral tonic-clonic seizures. The proband's ictal EEG showed clear left temporal seizure onset, and cerebral MRI revealed subtle left temporal changes (mild hypotrophy, slight blurring of the white and grey matter and hyperintensity) with corresponding left temporal mesial focal hypometabolism on FDG-PET. Genetic testing identified a missense variant, c.6631C>T (p.Arg2211Cys), in reelin repeat #5 in both patients, which markedly affected the secretion of the protein. The data from this family support previous findings indicating that reelin mutations are a cause of autosomal dominant lateral temporal lobe epilepsy which has a clinical spectrum that may also encompass drug-resistant epilepsy associated with mild MRI temporal changes.

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.

Epilepsy associated tumors: Review article.

Long-term epilepsy associated tumors (LEAT) represent a well known cause of focal epilepsies. Glioneuronal tumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly arising in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic network with complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation.

PDCD10 gene mutations in multiple cerebral cavernous malformations.

Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, intracerebral haemorrhages, and focal neurological deficits. Familial form shows an autosomal dominant pattern of inheritance with incomplete penetrance and variable clinical expression. Three genes have been identified causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3. Aim of this study is to report additional PDCD10/CCM3 families poorly described so far which account for 10-15% of hereditary cerebral cavernous malformations. Our group investigated 87 consecutive Italian affected individuals (i.e. positive Magnetic Resonance Imaging) with multiple/familial CCM through direct sequencing and Multiplex Ligation-Dependent Probe Amplification (MLPA) analysis. We identified mutations in over 97.7% of cases, and PDCD10/CCM3 accounts for 13.1%. PDCD10/CCM3 molecular screening revealed four already known mutations and four novel ones. The mutated patients show an earlier onset of clinical manifestations as compared to CCM1/CCM2 mutated patients. The study of further families carrying mutations in PDCD10/CCM3 may help define a possible correlation between genotype and phenotype; an accurate clinical follow up of the subjects would help define more precisely whether mutations in PDCD10/CCM3 lead to a characteristic phenotype.

Mild Lafora disease: clinical, neurophysiologic, and genetic findings.

We report clinical, neurophysiologic, and genetic features of an Italian series of patients with Lafora disease (LD) to identify distinguishing features of those with a slowly progressive course. Twenty-three patients with LD (17 female; 6 male) were recruited. Mean age (± SD) at the disease onset was 14.5 ± 3.9 years and mean follow-up duration was 13.2 ± 8.0 years. NHLRC1 mutations were detected in 18 patients; EPM2A mutations were identified in 5. Patients who maintained >10 years gait autonomy were labeled as "mild" and were compared with the remaining LD patients with a typical course. Six of 23 patients were mild and presented significantly delay in the age at onset, lower neurologic disability score at 4 years after the onset, less severe seizure phenotype, lower probability of showing both photoparoxysmal response on electroencephalography (EEG) and giant somatosensory evoked potentials, as compared to patients with typical LD. However, in both mild and typical LD patients, EEG showed disorganization of background activity and frequent epileptiform abnormalities. Mild LD patients had NHLRC1 mutations and five of six carried homozygous or compound heterozygous D146N mutation. This mutation was found in none of the patients with typical LD. The occurrence of specific NHLRC1 mutations in patients with mild LD should be taken into account in clinical practice for appropriate management and counseling.

Seizure outcome in surgically treated drug-resistant mesial temporal lobe epilepsy based on the recent histopathological classifications.

OBJECT: The study was performed to investigate the relation between seizure outcome after surgical treatment of mesial temporal lobe epilepsy (MTLE) and pathological findings, classified according to the recently proposed classifications of mesial temporal sclerosis (MTS), granule cell pathology (GCP), focal cortical dysplasia (FCD) and epilepsy-associated low-grade tumors (ELGT). METHODS: The authors analyzed data obtained in 120 consecutive cases involving patients presenting with drug-resistant MTLE, who underwent tailored anteromesial temporal lobe resection, and correlated seizure outcome with pathological findings. They identified 5 histopathological groups: Group 1-ELGT, alone or associated with other lesions (30 cases); Group 2-isolated FCD (17 cases); Group 3-MTS, with or without GCP (28 cases); Group 4-MTS associated with FCD, with or without GCP (37 cases); Group 5-other lesions (8 cases). RESULTS: Engel Class I outcome was observed in 83% of patients with ELGT (Class IA in 63%); in 59% of patients with isolated FCD, with FCD Type II showing a better prognosis than FCD Type I; in 82% of patients with isolated MTS (Class IA in 50%), with MTS Type 1a and MTS Type 1b showing a better prognosis than MTS Type 2 and patients with MTS and GCP having better postsurgical results than those with MTS without GCP. Engel Class I outcome was also achieved in 84% of patients with FCD associated with MTS (Engel Class IA in 62%); also in this group MTS 1a and MTS 1b associated with FCD showed a better prognosis than FCD associated with MTS 2. Finally, Engel Class I was also achieved in 2 patients with vascular malformation and in 1 with a temporal pole encephalocele. CONCLUSIONS: Patients with MTLE and ELGT, MTS, or MTS associated with FCD showed the best postsurgical seizure outcome (Engel Class I in more than 80% of cases), whereas only 63% of patients with isolated FCD achieved the same type of outcome. Interestingly, the analysis of seizure outcome in histopathological subtypes of FCD and of MTS showed different prognoses in the different pathological subgroups, with worse outcomes for atypical MTS, absence of GCP, and isolated FCD Type I.

Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families without LGI1 mutations.

PURPOSE: In relatively small series, autosomal dominant lateral temporal epilepsy (ADLTE) has been associated with leucine-rich, glioma-inactivated 1 (LGI1) mutations in about 50% of the families, this genetic heterogeneity being probably caused by differences in the clinical characteristics of the families. In this article we report the overall clinical and genetic spectrum of ADLTE in Italy with the aim to provide new insight into its nosology and genetic basis. METHODS: In a collaborative study of the Commission of Genetics of the Italian League Against Epilepsy (LICE) encompassing a 10-year period (2000-2010), we collected 33 ADLTE families, selected on the basis of the following criteria: presence of at least two members concordant for unprovoked partial seizures with prominent auditory and or aphasic symptoms, absence of any known structural brain pathology or etiology, and normal neurologic examination. The clinical, neurophysiologic, and neuroradiologic findings of all patients were analyzed and a genealogic tree was built for each pedigree. The probands' DNA was tested for LGI1 mutations by direct sequencing and, if negative, were genotyped with single-nucleotide polymorphism (SNP) array to search for disease-linked copy-number variation CNV. The disease penetrance in mutated and nonmutated families was assessed as a proportion of obligate carriers who were affected. KEY FINDINGS: The 33 families included a total of 127 affected individuals (61 male, 66 female, 22 deceased). The age at onset ranged between 2 and 60 years (mean 18.7 years). Ninety-one patients (72%) had clear-cut focal (elementary, complex, or secondarily generalized) seizures, characterized by prominent auditory auras in 68% of the cases. Other symptoms included complex visual hallucinations, vertigo, and déjà vu. Aphasic seizures, associated or not with auditory features, were observed in 20% of the cases, whereas tonic-clonic seizures occurred in 86% of the overall series. Sudden noises could precipitate the seizures in about 20% of cases. Seizures, which usually occurred at a low frequency, were promptly controlled or markedly improved by antiepileptic treatment in the majority of patients. The interictal electroencephalography (EEG) studies showed the epileptiform temporal abnormalities in 62% of cases, with a slight predominance over the left region. Magnetic resonance imaging (MRI) or computerized tomography (CT) scans were negative. LGI1 mutations (missense in nine and a microdeletion in one) were found in only 10 families (30%). The patients belonging to the mutated and not mutated groups did not differ except for penetrance estimate, which was 61.3% and 35% in the two groups, respectively (chi-square, p = 0.017). In addition, the disease risk of members of families with mutations in LGI1 was three times higher than that of members of LGI1-negative families (odds ratio [OR] 2.94, confidence interval [CI] 1.2-7.21). SIGNIFICANCE: A large number of ADLTE families has been collected over a 10-year period in Italy, showing a typical and homogeneous phenotype. LGI1 mutations have been found in only one third of families, clinically indistinguishable from nonmutated pedigrees. The estimate of penetrance and OR, however, demonstrates a significantly lower penetrance rate and relative disease risk in non-LGI1-mutated families compared with LGI1-mutated pedigrees, suggesting that a complex inheritance pattern may underlie a proportion of these families.

Seizure outcome of surgical treatment of focal epilepsy associated with low-grade tumors in children.

OBJECT: Low-grade tumor (LGT) is an increasingly recognized cause of focal epilepsies, particularly in children and young adults, and is frequently associated with cortical dysplasia. The optimal surgical treatment of epileptogenic LGTs in pediatric patients has not been fully established. METHODS: In the present study, the authors retrospectively reviewed 30 patients (age range 3-18 years) who underwent surgery for histopathologically confirmed LGTs, in which seizures were the only clinical manifestation. The patients were divided into 2 groups according to the type of surgical treatment: patients in Group A (20 cases) underwent only tumor removal (lesionectomy), whereas patients in Group B (11 cases) underwent removal of the tumor and the adjacent epileptogenic zone (tailored surgery). One of the patients, who underwent 2 operations, is included in both groups. Follow-up ranged from 1 to 17 years. RESULTS: Sixteen (80%) of 20 patients in Group A had an Engel Class I outcome. In this group, 3 of 4 patients who were in Engel Classes II and III had temporomesial lesions. All patients in Group B had temporomesial tumors and were seizure free (Engel Class I). In this series, in temporolateral and extratemporal tumor locations, lesionectomy yielded a good seizure outcome. In addition, a young age at seizure onset (in particular < 4 years) was associated with a poor seizure outcome. CONCLUSIONS: Tailored resection in temporomesial LGTs was associated with excellent seizure outcome, indicating that an adequate presurgical evaluation including extensive neurophysiological evaluation (long-term videoelectroencephalography monitoring) to plan appropriate surgical strategy is advised.

Genetics of epilepsy and relevance to current practice.

Genetic factors are likely to play a major role in many epileptic conditions, spanning from classical idiopathic (genetic) generalized epilepsies to epileptic encephalopathies and focal epilepsies. In this review we describe the genetic advances in progressive myoclonus epilepsies, which are strictly monogenic disorders, genetic generalized epilepsies, mostly exhibiting complex genetic inheritance, and SCN1A-related phenotypes, namely genetic generalized epilepsy with febrile seizure plus and Dravet syndrome. Particular attention is devoted to a form of familial focal epilepsies, autosomal-dominant lateral temporal epilepsy, which is a model of non-ion genetic epilepsies. This condition is associated with mutations of the LGI1 gene, whose protein is secreted from the neurons and exerts its action on a number of targets, influencing cortical development and neuronal maturation.

Oligodendroglial hamartoma: a potential source of misdiagnosis for oligodendroglioma.

Various subtypes of intracerebral hamartomas, associated with seizure disorders, have long been described. We describe a cerebral hamartoma placed in the left frontal lobe, associated with drug-resistant epilepsy, composed exclusively of mature oligodendroglial cells. The patient was a 27-year-old right-handed male presenting with severe epileptic encephalopathy and symptoms of behavior dysfunction (disinhibition, rage attacks) associated with a left frontal lesion. Magnetic resonance imaging revealed a small area iso-hypointense compared to the gray matter in T1-weighted sequences not enhancing after gadolinium contrast injection in the left frontal site. On histology, a cortical lesion composed of large aggregates of oligodendroglial cells, with round central nuclei and clear perinuclear halos, was observed. Neither mitotic figures nor necrosis were present. Reactivity for Ki67 and P53 was not found. The lesion was well demarcated from the adjacent brain parenchyma and perineuronal satellitosis was not observed in the cortex. In conclusion, albeit extremely rare, recognition of oligodendroglial hamartoma and its distinction from other epileptogenic lesions as dysembryoplastic neuroepithelial tumor or above all oligodendroglioma have important therapeutic and prognostic implications.