Long-term cognitive outcome after radiosurgery in epileptic hypothalamic hamartomas and review of the literature.

OBJECTIVE: Epileptic patients with hypothalamic hamartoma (HH) frequently present cognitive impairments. Surgical techniques aiming at HH can be very efficient for epilepsy relief and cognitive improvement but are also demonstrated to carry a significant risk of additional reduction in memory function in these already disabled patients. Gamma knife radiosurgery (GKS) offers an efficient minimally invasive procedure. We evaluated the effect of stereotactic radiosurgery on cognitive outcome. METHODS: We designed a prospective single-center case series study. Thirty-nine epileptic patients (median age = 17 years, range = 4-50) with HH underwent preoperative and postoperative testing of intelligence quotient (IQ; all patients), including a working memory component, and other memory function testing (for patients ≥16 years old). All patients were prospectively evaluated and underwent complete presurgical and postsurgical clinical, electrophysiological, endocrinal, and visual assessments. In all patients, the postoperative assessment was performed at least 3 years after radiosurgery. We explored what variables correlate with cognitive outcome. Literature review was done for other surgical techniques and their risks for cognitive complications after surgery. RESULTS: No decline was observed in intellectual ability (including working memory) after GKS, and no memory decline was seen in adults. We observed significant improvement (>1 SD in z-score) in working memory index (46%) and processing speed index (35%), as well as improvement in full-scale IQ (24%), verbal comprehension index (11%), perceptual organization index (21%), verbal learning (20%), and visual learning (33%). Before GKS, the probability of seizure cessation was higher in patients with higher cognitive performance. After GKS, the cognitive improvement was significantly higher in the seizure-free patients compared to the non-seizure-free patients. SIGNIFICANCE: We found clear cognitive improvement in a high percentage of patients but importantly no significant decline in intellectual ability (including working memory) and no decline in memory in adult patients 3 years after GKS. GKS compares favorably to the other surgical techniques in terms of cognitive outcome, with similar seizure freedom.

Safety and efficacy of Gamma Knife radiosurgery in hypothalamic hamartomas with severe epilepsies: A prospective trial in 48 patients and review of the literature.

Epilepsies associated with hypothalamic hamartomas (HHs) are frequently drug resistant with severe psychiatric and cognitive comorbidities. We performed a prospective trial to evaluate the safety and efficacy of Gamma Knife radiosurgery (GKS). Between October 1999 and October 2007, a total of 57 patients were investigated, included and treated by GKS in Timone University Hospital. Preoperative workup and 3-year postoperative evaluation consisted of seizure diary, neuropsychological, psychiatric, endocrinologic, visual field, and visual acuity examinations. Follow-up of >3 years was available for 48 patients. Topologic type was type I in 11 patients, type II in 15, type III in 17, type IV in one, type V in one, type VI in one, and mixed type in 2. The median marginal dose was 17 Gy (min 14 and max 25 Gy). The median target volume was 398 mm3 (28-1,600 mm3 ). Due to partial results, 28 patients (58.3%) required a second treatment. The median follow-up was 71 months (36-153 months). At last follow-up, the rate of Engel class I outcome was 39.6%, Engel class II was 29.2% (I+II 68.8%), and Engel class III was 20%. Global psychiatric comorbidity was considered cured in 28%, improved in 56%, stable in 8%, and continued to worsen in 8%. No permanent neurologic side effect was reported (in particular, no memory deficit). Nondisabling transient poikilothermia was observed in three patients (6.2%). A transient increase of seizure frequency was reported in 8 patients (16.6%) with a median duration of 30 days (9-90 days). Microsurgery was proposed because of insufficient efficacy of GKS in seven patients (14.5%) with a postoperative Engel class I-II in 28.6%. This prospective trial demonstrates very good long-term safety and efficacy of GKS for 2 patients. Beyond seizure reduction, the improvement of psychiatric and cognitive comorbidities along with better school performance and social functioning, being better socially integrated, having friends having a social life, working, participating to group activities turn out to be major benefits of GKS in this group of patients with frequently catastrophic epilepsy.

Anti-tumor necrosis factor alpha therapy (adalimumab) in Rasmussen's encephalitis: An open pilot study.

OBJECTIVE: Rasmussen's encephalitis (RE) is a severe chronic inflammatory brain disease affecting one cerebral hemisphere and leading to drug-resistant epilepsy, progressive neurologic deficit, and unilateral brain atrophy. Hemispherotomy remains the gold standard treatment but causes permanent functional impairment. No standardized medical treatment protocol currently exists for patients prior to indication of hemispherotomy, although some immunotherapies have shown partial efficacy with functional preservation but poor antiseizure effect. Some studies suggest a role for tumor necrosis factor alpha (TNF-α) in RE pathophysiology. METHODS: We report an open-label study evaluating the efficacy and the safety of anti-TNF-α therapy (adalimumab) in 11 patients with RE. The primary outcome criterion was the decrease of seizure frequency. The secondary outcome criteria were neurologic and cognitive outcomes and existence of side effects. RESULTS: Adalimumab was introduced with a median delay of 31 months after seizure onset (range 1 month to 16 years), and follow-up was for a median period of 18 months (range 9-54 months). There was a significant seizure frequency decrease after adalimumab administration (from a median of 360 to a median of 32 seizures per quarter, p ≤ 0.01). Statistical analysis showed that adalimumab had a significant intrinsic effect (p < 0.005) independent from disease fluctuations. Five patients (45%) were found to have sustained improvement over consecutive quarters in seizure frequency (decrease of 50%) on adalimumab. Three of these five patients also had no further neurocognitive deterioration. Adalimumab was well tolerated. SIGNIFICANCE: Our study reports efficacy of adalimumab in terms of seizure frequency control. In addition, stabilization of functional decline occurred in three patients. This efficacy might be particularly relevant for atypical slowly progressive forms of RE, in which hemispherotomy is not clearly indicated. Due to our study limitations, further studies are mandatory to confirm these preliminary results.

Cognitive and adaptive evaluation of 21 consecutive patients with Dravet syndrome.

In order to assess the cognitive and adaptive profiles of school-aged patients with Dravet syndrome (DS), we proposed to evaluate the intelligence and adaptive scores in twenty-one 6- to 10-year-old patients with DS followed in our institution between 1997 and 2013. Fourteen patients were tested using the Wechsler Intelligence Scale for Children (WISC) and the Vineland Adaptive Behavioral Scales (VABS); 6 patients could not be tested with the WISC and were tested with the VABS only, and one was tested with the WISC only. Data regarding the epilepsy were retrospectively collected. Statistical analysis (Spearman rank order and Pearson correlation coefficient) was used to correlate early epilepsy characteristics with the cognitive and adaptive scores. Sodium channel, neuronal alpha-subunit type 1 (SCN1A) was mutated in 19 out of 21 patients. After the age of 6years, none of the DS patients had a normal intelligence quotient (IQ) using WISC (age at the testing period: mean=100±5; median=105months; mean total IQ=47±3; n=15). Only five patients had a verbal and/or a non verbal IQ of more than 60 (points). Their cognitive profile was characterized by an attention deficit, an inability to inhibit impulsive responses, perseverative responses and deficit in planning function. Administering the Vineland Adaptive Behavioral Scales in the same period, we showed that socialization skills were significantly higher than communication and autonomy skills (age at the testing period: mean=100±4; median=100months; n=20). We did not find any significant correlation between the IQ or developmental quotient assessed between 6 and 10years of age and the quantitative and qualitative parameters of epilepsy during the first two years of life in this small group of patients. Despite an overall moderate cognitive deficit in this group of patients, the Vineland Adaptive Behavioral Scales described an adaptive/behavioral profile with low communication and autonomy capacities, whereas the socialization skills were more preserved. This profile was different from the one usually found in young patients with autism and may require specific interventions.

Reversible antisocial behavior in ventromedial prefrontal lobe epilepsy.

Frontal lobe dysfunction is known to be associated with impairment in social behavior. We investigated the link between severe pharmacoresistant frontal lobe epilepsy and antisocial trait. We studied four patients with pharmacoresistant epilepsy involving the prefrontal cortex, presenting abnormal interictal social behavior. Noninvasive investigations (video-EEG, PET, MRI) and intracerebral recording (stereoelectroencephalography (SEEG)) were performed as part of a presurgical assessment. Comprehensive psychiatric and cognitive evaluation was performed pre- and postoperatively for frontal lobe epilepsy, with at least 7years of follow-up. All patients shared a characteristic epilepsy pattern: (1) chronic severe prefrontal epilepsy with daily seizures and (2) an epileptogenic zone as defined by intracerebral recording involving the anterior cingulate cortex, ventromedial PFC, and the posterior part of the orbitofrontal cortex, with early propagation to contralateral prefrontal and ipsilateral medial temporal structures. All patients fulfilled the diagnostic criteria (DSM-IV) of antisocial personality disorder, which proved to be reversible following seizure control. Pharmacoresistant epilepsy involving a prefrontal network is associated with antisocial personality. We hypothesize that the occurrence of frequent seizures in this region over a prolonged period produces functional damage leading to impaired prefrontal control of social behavior. This functional damage is reversible since successful epilepsy surgery markedly improved antisocial behavior in these patients. The results are in line with previous reports of impairment of social and moral behavior following ventromedial frontal lobe injury.

Hippocampal intracerebral evoked potentials as a marker of its functionality in drug-resistant epilepsy.

OBJECTIVES: To assess hippocampal function during stereoelectroencephalography (SEEG) investigations through the study of the medial temporal lobe event-related potential (ERP) MTL-P300. METHODS: We recorded the MTL-P300 during a visual oddball task, using hippocampal electrodes implanted for SEEG in 71 patients, in a preoperative epilepsy investigation. The presence of an MTL-P300 and its amplitude were correlated with hippocampal involvement during seizures and memory function. RESULTS: Analysis using ROC curves revealed that an MTL-P300 amplitude below -46 µV, has a specificity of 93.3% in detecting the epileptogenic zone, and absence of the MTL-P300 in the left hippocampus of patients with typical language organization was associated with marked alteration of verbal memory scores. There was a significant correlation between performance in non-verbal memory tests and the amplitude of the MTL-P300 in the right hippocampus of patients with left hemispheric seizures (immediate visual recall: r = 0.67, p = 0.005; delayed visual recall: r = 0.56, p = 0.025). Using a linear regression, we confirmed that the absence of the MTL-P300 in the left hippocampus, the involvement of the left hippocampus during seizures, and the duration of epilepsy were predictors of verbal memory deficits. CONCLUSION: Analysis of the MTL-P300 during SEEG recording provides relevant information for the analysis of hippocampal functionality and can help to localize the epileptogenic zone.

Epileptic hypothalamic hamartomas impact of topography on clinical presentation and radiosurgical outcome.

INTRODUCTION: Evidence exists for the role of the hypothalamic hamartoma's topography as a determinant for the clinical presentation. How the hamartoma relation to the hypothalamic structures can make clinical presentations, severity and surgery outcomes different from patient to patient is largely unknown. Our aim was to analyze the effect of fine anatomical topography on clinical spectrum and radiosurgery outcome. METHODS: Forty-eight epileptic patients with hypothalamic hamartoma were treated by Gamma Knife Surgery and were reviewed for fine topography and morphology using magnetic resonance neuroimaging. We evaluated different topographic patterns; contact to prominent structures (the mammillary body, tuber cinereum and pituitary stalk), the degree of involvement within sagittally-oriented regions, (mammillary, tuberal, and supra optic) coronally-oriented zones (periventricular, medial, and lateral), lesion dimensions (length, width, and height),and volumes (total, intra-hypothalamic, and extra-hypothalamic volumes). This data were statistically analysed for correlation with all clinical variables and epilepsy surgery outcome. We reviewed all the classification protocols in the literature. RESULTS: Focal onset impaired awareness seizures started at an earlier age of onset with larger hypothalamic hamartoma volume and dimensions. Lateral extension within the hypothalamus was associated with more severe epilepsy, higher seizure frequency, more severe psychiatric comorbidity, hetero-aggression, hyperkinesia, and school difficulties. Presence of precocious puberty was positively correlated to anterior-posterior extension; tuberal region involvement, hypothalamic hamartoma volume, and type III-VI. Larger hypothalamic hamartoma presented precocious puberty at an earlier age of onset. After Gamma Knife Surgery, epilepsy outcome was better and rapid when lesion is smaller. Post-radiosurgical transient increased seizures were present when the mammillary region was more involved. CONCLUSION: Clinical presentation of epileptic hypothalamic hamartoma is significantly affected by fine topography patterns and invaded hypothalamic areas. Gamma Knife Radiosurgery effect is better and rapid in smaller hamartoma (Type I-III) and seizure outcome was not affected by the invaded hypothalamic areas.

Intellectual outcome from 1 to 5 years after epilepsy surgery in 81 children and adolescents: A longitudinal study.

OBJECTIVE: This longitudinal study aimed to measure the time course of intellectual changes after pediatric focal resective epilepsy surgery and to identify their predictors. METHODS: We analyzed a cohort of 81 school-aged children with focal epilepsy and intractable seizures who underwent neurosurgery (focal resection) from 2000 to 2018 in La Timone Hospital (Marseille). Neuropsychological assessments were carried out before and then 1, 2, 3, and 5 years after epilepsy surgery. RESULTS: Eighty-one patients with a median age at surgery of 13.74 years [4.25] were enrolled. Overall, 45 of the 81 (55%) recruited patients were improved after the surgery on at least one of the five domains of the Wechsler Intelligence Scale. Temporal lobe localization and postoperative seizure freedom were the main prognostic factors impacting intellectual outcome (improvement and decline) after epilepsy surgery. Younger patients at surgery were less likely to have a postoperative IQ decline. Intellectual improvement after epilepsy surgery could be delayed for up to 5 years after surgery and concerned all intellectual domains except the Verbal Comprehension Index (VCI). Intellectual decline after epilepsy surgery occurred mainly during the first two years after the surgery and was reflected in full-scale intelligence quotient (FSIQ) and Working Memory Index (WMI). CONCLUSIONS: Our study points out that children and adolescents with TLE who achieved freedom from seizure after epilepsy surgery are the leading candidates for achieving postoperative intellectual improvement. This enhancement in intellectual function shows a long time course, whereas intellectual decline is evidenced earlier.

Brain regions underlying word finding difficulties in temporal lobe epilepsy.

Word finding difficulties are often reported by epileptic patients with seizures originating from the language dominant cerebral hemisphere, for example, in temporal lobe epilepsy. Evidence regarding the brain regions underlying this deficit comes from studies of peri-operative electro-cortical stimulation, as well as post-surgical performance. This evidence has highlighted a role for the anterior part of the dominant temporal lobe in oral word production. These conclusions contrast with findings from activation studies involving healthy speakers or acute ischaemic stroke patients, where the region most directly related to word retrieval appears to be the posterior part of the left temporal lobe. To clarify the neural basis of word retrieval in temporal lobe epilepsy, we tested forty-three drug-resistant temporal lobe epilepsy patients (28 left, 15 right). Comprehensive neuropsychological and language assessments were performed. Single spoken word production was elicited with picture or definition stimuli. Detailed analysis allowed the distinction of impaired word retrieval from other possible causes of naming failure. Finally, the neural substrate of the deficit was assessed by correlating word retrieval performance and resting-state brain metabolism in 18 fluoro-2-deoxy-d-glucose-Positron Emission Tomography. Naming difficulties often resulted from genuine word retrieval failures (anomic states), both in picture and in definition tasks. Left temporal lobe epilepsy patients showed considerably worse performance than right temporal lobe epilepsy patients. Performance was poorer in the definition than in the picture task. Across patients and the left temporal lobe epilepsy subgroup, frequency of anomic state was negatively correlated with resting-state brain metabolism in left posterior and basal temporal regions (Brodmann's area 20-37-39). These results show the involvement of posterior temporal regions, within a larger antero-posterior-basal temporal network, in the specific process of word retrieval in temporal lobe epilepsy. A tentative explanation for these findings is that epilepsy induces functional deafferentation between anterior temporal structures devoted to semantic processing and neocortical posterior temporal structures devoted to lexical processing.

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms.

A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms.

Description of a family with a novel progressive myoclonus epilepsy and cognitive impairment.

We report a family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. The diagnosis of Unverricht-Lundborg disease and all other known causes of progressive myoclonus epilepsies were excluded by specific laboratory tests and molecular analysis.

Predictive Factors of Surgical Outcome in Frontal Lobe Epilepsy Explored with Stereoelectroencephalography.

BACKGROUND: Resective surgery established treatment for pharmacoresistant frontal lobe epilepsy (FLE), but seizure outcome and prognostic indicators are poorly characterized and vary between studies. OBJECTIVE: To study long-term seizure outcome and identify prognostic factors. METHODS: We retrospectively analyzed 42 FLE patients having undergone surgical resection, mostly preceded by invasive recordings with stereoelectroencephalography (SEEG). Postsurgical outcome up to 10-yr follow-up and prognostic indicators were analyzed using Kaplan-Meier analysis and multivariate and conditional inference procedures. RESULTS: At the time of last follow-up, 57.1% of patients were seizure-free. The estimated chance of seizure freedom was 67% (95% confidence interval [CI]: 54-83) at 6 mo, 59% (95% CI: 46-76) at 1 yr, 53% (95% CI: 40-71) at 2 yr, and 46% (95% CI: 32-66) at 5 yr. Most relapses (83%) occurred within the first 12 mo. Multivariate analysis showed that completeness of resection of the epileptogenic zone (EZ) as defined by SEEG was the main predictor of seizure outcome. According to conditional inference trees, in patients with complete resection of the EZ, focal cortical dysplasia as etiology and focal EZ were positive prognostic indicators. No difference in outcome was found in patients with positive vs negative magnetic resonance imaging. CONCLUSION: Surgical resection in drug-resistant FLE can be a successful therapeutic approach, even in the absence of neuroradiologically visible lesions. SEEG may be highly useful in both nonlesional and lesional FLE cases, because complete resection of the EZ as defined by SEEG is associated with better prognosis.

Reading abilities and cognitive functions of children with epilepsy: influence of epileptic syndrome.

Children with epilepsy are at risk of developing learning disorders. To explore the influence of the epileptic syndrome on reading abilities, we have compared the neuropsychological profile of 12 children with benign idiopathic epilepsy with rolandic spikes, 10 with temporal lobe epilepsy and 12 with idiopathic generalized epilepsy. Children underwent a selection of standardised tests designed to assess: oral language, reading, short-term memory, attention and behavioural adjustment. Analysis of variance was adjusted according to age of onset of the epileptic syndrome, duration of the syndrome, and performance IQ for each group. Children with temporal lobe epilepsy (TLE) had significantly lower scores for reading speed and comprehension, but epileptic variables (the age of onset of epilepsy, duration and activity of epilepsy) had influenced academic performances. In the TLE group there was a clear effect of the topography of the epileptic foci (left-side TLE vs. right-side TLE) on reading profile. Furthermore, the effect of epileptic syndromes was found in phonological, semantic and verbal working memory deficits in the TLE group. To a lesser extent children with idiopathic generalized epilepsy (IGE) also exhibit cognitive deficit. The results of the present study lend support to epilepsy-specific patterns of neuropsychological dysfunction in children that should be considered to improve remediation of academic underachievement in these populations.

An unusual case of neurocutaneous melanosis.

The neurocutaneous melanosis (NCM) is a rare, neuroectodermal dysplasia defined by the association of giant or multiple, nonmalignant pigmented cutaneous nevi with leptomeningeal melanosis or melanoma. As a rule, the cerebral pathological substratum is characterized by a melanocytic infiltration of the leptomeninges, often leading to hydrocephalus. The most frequent clinical symptomatology starts early in life, with convulsive seizures, psychomotor delay, intracranial hyperpression: the prognosis is severe. Malignant melanomas can also occur. One 21 years-old patient affected by NCM with a giant bathing nevus and epilepsy is reported. Her psychomotor development was slightly delayed. Academic progress was disturbed by the frequency of seizures and the multiple dermatological surgeries, and she remained at the elementary school level. Her epilepsy appeared at seven years and became pharmacoresistant. It was a focal, left temporal epilepsy. Neuroimaging investigations were performed repeatedly, and demonstrated the progressive appearance of parenchymal lesions with T1 and T2 shortening, without contrast enhancement, at the pons (11 years), the two hippocampi (14 years), and of an atrophy of the cerebellum and the brainstem (19 years). No hydrocephalus, tumoral aspect, or meningeal involvement were demonstrated. This patient's case is peculiar because her neurological symptomatology consists only of focal epilepsy, unrelated to a tumor, with moderate cognitive impairment despite a rather long course of the disease. Her evolution raises the question of condidency to surgical treatment.

Cortical involvement in focal epilepsies with epileptic spasms.

The pathophysiological mechanisms of epileptic spasms are still poorly understood. The role of subcortical structures has been suggested on the basis of non-localized EEG features and from experimental data. The description of asymmetric spasms associated with lateralized EEG patterns has challenged this view and raises the possibility of a cortical origin. This study investigated the cortical organization of partial seizures associated with epileptic spasms in children undergoing intracerebral EEG recordings for presurgical evaluation. Eleven children with drug resistant epileptic spasms and for whom depth electrode recordings were performed were retrospectively studied. In all children several features suggested a focal origin. Cortical involvement was studied using the "Epileptogenicity Index" (EI). A focal origin was finally demonstrated in 10/11 patients. Seven patients demonstrated pre-ictal changes in the seizure onset zone area. EI analysis showed maximal values in the temporal (n=5), parietal (n=1) or frontal (n=5) cortices. EEG changes were also observed in the premotor cortex during spasms in patients with frontal or parietal seizures and in 3/5 patients with temporal lobe seizures. Good surgical outcome (class I or II) was obtained in 7/10 patients. Seizures associated with epileptic spasms may originate from various cortical regions. Premotor/motor cortices are probably involved in determining ictal clinical changes.

Absence epilepsy with onset before age three years: a heterogeneous and often severe condition.

PURPOSE: The classification of epilepsies and epileptic syndromes recognizes three syndromes with typical absences [TA, i.e., childhood and juvenile absence epilepsies (CAE and JAE), and epilepsy with myoclonic absences (EMA), none of which is characterized by onset in early childhood]. Although several other forms of absence epilepsies have been described recently, none concerns infants and very young children, and little is known about the nosology and prognosis of early-onset absences. METHODS: We retrospectively selected all cases with onset of absences as the only or major seizure type before age 3 years and >/=2 years of follow-up among cases newly referred between 1986 and 2002. Neuropsychological assessments (generally IQ measure), behavior patterns, and schooling situations were reviewed for each child. RESULTS: We found 10 patients (7 F, 3 M). No child had sensory or motor deficits: neuroimaging was performed in nine and was normal in eight, with aspecific findings in one. Only two could be characterized as CAE and EMA, respectively, both with seizure control and a good cognitive outcome. Among the remaining eight cases, four had a fairly homogeneous presentation with predominantly brief absences and clearly asymmetric interictal EEGs. All eight had neuropsychological and/or behavioral difficulties. Three had full seizure control, and five, persisting absences, with a follow-up ranging between 2 years 8 months to 9 years 4 months; only one child was older than 12 years. CONCLUSIONS: Great heterogeneity exists among absence epilepsies of early onset, which are rare conditions. Only a few patients can be categorized into well-known syndromes. The overall prognosis is poor. Early onset of absences is uncommon, and multicenter studies should help clarify the nosology and prognosis.