José Augusto Bragatti

The phenomenon of Forced Normalization (FN) was first described by Landolt in 1953, who described the disappearance of epileptiform discharges in the EEG of patients with epilepsy, concomitant with the development of psychotic symptoms. Later, Tellenbach coined the term “alternative psychosis” referring specifically to the alternation between clinical phenomena. Finally, in 1991, Wolf observed a degenerative process involved in the phenomenon, which he called “paradoxical normalization.” Initially, FN was explained through experimental models in animals and the demonstration of the kindling phenomenon, in its electrical and pharmacological subdivisions. At this stage of research on the epileptic phenomenon, repetitive electrical stimuli applied to susceptible regions of the brain (hippocampus and amygdala) were considered to explain the pathophysiological basis of temporal lobe epileptogenesis. Likewise, through pharmacological manipulation, especially of dopaminergic circuits, psyc...

The recognition and treatment of psychosis in persons with epilepsy (PWE) is recommended with the apparent dilemma between treating psychosis and opening the possibility of exacerbating seizures. The pooled prevalence estimate of psychosis in PWE is 5.6%. It has been proposed that a 'two hit' model, requiring both aberrant limbic activity and impaired frontal control, may account for the wide range of clinical phenotypes. The role of antiepileptic drugs in psychosis in PWE remains unclear. Alternating psychosis, the clinical phenomenon of a reciprocal relationship between psychosis and seizures, is unlikely to be an exclusively antiepileptic drug-specific phenomenon but rather, linked to the neurobiological mechanisms underlying seizure control. Reevaluation of antiepileptic treatment, including the agent/s being used and degree of epileptic seizure control is recommended. The authors found very few controlled studies to inform evidence-based treatment of psychosis in PWE. H...

The NTRK2 gene encodes a member of the neurotrophic tyrosine kinase receptor family known as TrkB. It is a membrane-associated receptor with signaling and cellular differentiation properties that has been involved in neuropsychiatric disorders, including epilepsy. We report here the frequencies of NTRK2 allele variants in patients with temporal lobe epilepsy (TLE) compared to controls without epilepsy and explore the impact of these polymorphisms on major clinical variables in TLE. A case-control study comparing the frequencies of the NTRK2 gene polymorphisms beween 198 TLE Caucasian patients and 200 matching controls without epilepsy. In a second step, the impact of allelic variation on major clinical and electroencephalographic epilepsy variables was evaluated in the group of TLE patients. The following polymorphisms were determined by testing different regions of the NTRK2 gene: rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. To correct for multiple correlations the level of significance was set at p<0.01. Patients with TLE showed a statistical trend for increase of the T/T genotype in rs10868235 compared to control (O.R.=1.90; 95%CI=1.17-3.09; p=0.01). Homozygous patients for the A allele in rs1443445 had earlier mean age at onset of seizures, p=0.009 (mean age of 16.6 versus 22.4years). We also observed that the T allele in rs3780645 was more frequent in patients who needed polytheraphy for seizure control than in patients on monotherapy, (O.R.=4.13; 95%CI=1.68-10.29; p=0.001). This finding may reflect an increased difficulty to obtain seizure control in this group of patients. No additional differences were observed in this study. Patients with epilepsy showed a trend for a difference in rs10868235 allelic distribution compared to controls without epilepsy. NTRK2 variability influenced age at seizure onset and the pharmacological response to seizure control. As far as we know, this is the first study showing an association between NTKR2 allelic variants in human epilepsy. We believe that further studies in this venue will shade some light on the molecular mechanisms involved in epileptogenesis and in the clinical characteristics of epilepsy.

Coma is a relatively common condition in the pediatric intensive care unit. Although the principles of diagnosis and management are basically the same for both children and adults, there are some age-specific aspects related to infants and children under 16 years of age that influences the pediatric intensive care practitioner’s conduct. Several aspects regarding neuroplasticity, raised intracranial pressure and epileptogenesis in the immature brain are considered in this article. Importantly, the role of new technologies employed for neurophysiologic monitoring is also reviewed. The aim of this article is to evaluate the main issues comprising the comatose state in childhood and their differences from the same condition in adulthood. Several differences in the physiology of immature brains can affect clinical and neurophysiologic expression in a disorder of consciousness and may need special proceedings for its management. Future perspectives in the field are referred in the final ...

Cefepime is a widely used antibiotic. However, it can cause encephalopathy, which has been increasingly described in the literature, occurring mainly in patients with impaired renal function. The primary objective in this study was to measure the incidence of cefepime-induced encephalopathy and determine potential risk factors for its occurrence. In the period from February 2005 to February 2006, a prospective cohort study was conducted, which followed 498 patients using cefepime. Other metabolic problems were ruled out for all patients with clinical suspicion of encephalopathy and, when cefepime was the probable cause, electroencephalographic (EEG) tests were performed to assist in the diagnosis, with the first performed during cefepime use and another performed at least 48 hours following drug discontinuation and/or clinical improvement. Among patients selected for this study (n=498), 5 were diagnosed with cefepime-induced encephalopathy, thus indicating a cumulative incidence of ...

Alpha coma, an EEG pattern characterized by diffuse or widespread rhythmic activity in the alpha frequency band, is typically recorded in patients with profound coma and is frequently associated with severe neurological conditions. The most common etiologic factors of this pattern are hypoxic-ischemic encephalopathy, encephalitis, head trauma, metabolic disorders, and drug overdose. Reports of alpha coma pattern in children are relatively common. Clinical significance, both in children and adults, is variable, and highly dependent on etiology. The objective of this article is to report a clinical case of alpha coma pattern in a child with neuroblastoma. The EEG pattern was recorded during the evolution of treatment, secondary to complicating septic encephalopathy. The alpha coma pattern was replaced by a normal trace following a favorable outcome after sepsis resolution.

Psychiatric comorbidities are frequent in temporal lobe epilepsy (TLE), and symptoms of these comorbidities may be related to epilepsy activity. Here we evaluated interictal EEG activity in TLE patients with or without psychiatric comorbidities. A cohort study of 78 patients with TLE, with evaluation of wake/sleep interictal scalp EEG. All subjects were submitted to a psychiatric structured clinical interview (SCID) for the diagnosis of lifetime psychiatric comorbidities. Three major diagnostic categories were studied: mood disorders, anxiety disorders, and psychosis. We then evaluated differences in interictal EEG activity between patients with and without these psychiatric comorbidities. Infrequent EEG interictal spikes, defined as less than one event per minute, were significantly associated with mood disorders in TLE (p=0.02). Low intensity seizure disorder has been associated with a decrease in interictal EEG discharges and with an increase in psychiatric symptoms in TLE, a phenomenon known as forced normalization. In our study, we observed a low interictal spike frequency on EEG in TLE patients with mood disorders. A low spike index might be a neurophysiological marker for depression in temporal lobe epilepsy.

Psychiatric comorbidities are frequent in temporal lobe epilepsy (TLE), and symptoms of these comorbidities may be related to epilepsy activity. Here we evaluated interictal EEG activity in TLE patients with or without psychiatric comorbidities. A cohort study of 78 patients with TLE, with evaluation of wake/sleep interictal scalp EEG. All subjects were submitted to a psychiatric structured clinical interview (SCID) for the diagnosis of lifetime psychiatric comorbidities. Three major diagnostic categories were studied: mood disorders, anxiety disorders, and psychosis. We then evaluated differences in interictal EEG activity between patients with and without these psychiatric comorbidities. Infrequent EEG interictal spikes, defined as less than one event per minute, were significantly associated with mood disorders in TLE (p=0.02). Low intensity seizure disorder has been associated with a decrease in interictal EEG discharges and with an increase in psychiatric symptoms in TLE, a phenomenon known as forced normalization. In our study, we observed a low interictal spike frequency on EEG in TLE patients with mood disorders. A low spike index might be a neurophysiological marker for depression in temporal lobe epilepsy.

Introdução Transtornos psiquiátricos são freqüentes em pacientes epilépticos, porém, a prevalência de comor-bidades psiquiátricas pode variar conforme a metodo-logia utilizada ea população estudada. Ainda estão faltando estudos bem controlados, com instrumentos diagnósticos ...

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Background: Few previous investigations have assessed neurobiological substrates for differentiating Attention-Deficit/Hyperactivity Disorder (ADHD) types through the use of modern neuroimaging techniques. Methods: We assessed the neurometabolic profile in frontal-striatal-thalamic right and left regions through 1H-magnetic resonance spectroscopy (1H-MRS) in three groups of subjects (age range: 15-24 years' old): ADHD inattentive type (ADHD-I; n 10), ADHD combined type (ADHD-C; n =10) and non-ADHD controls (n 12). Compounds that can be visualized with 1H-MRS include N-ace-tyl-aspartate (NAA), glutamate/glutamine/γ-aminobutyric acid (Glx), creatinine/phosphocreatine(Cr), and choline compounds (Cho). Results: Major differences were detected in metabolic ratios in subjects with ADHD-C compared with those with ADHD-I and controls, even after adjustments for comor-bidity. Subjects with ADHD-C showed a lower mI/Cr ratio in the right ventromedial prefrontal cortex (VMPFC) than controls (p 0.004), higher Cho/Cr ratio in the left pulvinar (thalamus posterior) than the ADHD-I group (p 0.02), and higher Glx/Cr ratio in left putamen nucleus than both individuals with ADHD-I and controls (p=0,049). No differences were detected between subjects with ADHD-I and non-ADHD controls. NAA/Cr ratio differed between patients and controls in the left VMPFC only when all ADHD subjects were grouped together (p=0.03). Conclusions: Our findings corroborate previous results

RESUMO-Cefepime, uma cefalosporina de quarta geração, com amplo espectro de ação, é um antibiótico largamente utilizado no tratamento de infecções graves em ambientes hospitalares. O registro de segurança deste fármaco é considerado favorável. Vários casos de encefalopatia grave, associada ao uso de cefepime, reversível, foram descritos recentemente. No presente artigo, descrevemos sete casos de encefalopatia induzida por cefepime, com achados eletroencefalográficos (EEG) característicos, que apresentaram reversão do quadro com a suspensão da droga. As relações do padrão EEG encontrado nestes pacientes com estado epiléptico não-convulsivo são consideradas, bem como a possibilidade de enquadrar os pacientes estudados na entidade " encefalopatia epileptiforme ". PALAVRAS-CHAVE: encefalopatia epileptiforme, padrão EEG periódico, estado epiléptico não-convulsivo, neurotoxicidade, cefepime. Cefepime-induced encephalopathy : clinical and electroencephalographic features in seven patients ABSTRACT-Cefepime, a fourth-generation cephalosporin, with large antibacterial spectrum, is a commonly used antibiotic for the treatment of serious hospitalar infections. Its security report is considered favourable. Recently, many cases of a severe and reversible cefepime-induced encephalopathy were described. In this p a p e r, we report seven patients with reversible cefepime-induced encephalopathy, with a peculiar EEG pattern, characterized by semiperiodic diffuse triphasic waves. We discuss the EEG abnormalities found and their association with nonconvulsive status epilepticus. KEY WORDS: epileptiform encephalopathy, periodic EEG pattern, nonconvulsive status epilepticus, neurotoxicity, cefepime.

period preceding the fatal seizure, compared with values measured one day and six month before, and also higher than the pre-ictal values in a group of 10 patients with generalised tonic-clonic seizures. This unfortunate case documented during video-EEG monitoring indicates that seizure-induced cardiac dysrhythmia can lead to SUDEP, and suggests that patients with increased parasympathetic activation in the pre-ictal period might have an increased risk of SUDEP in the period following the seizure. Question: Deep brain stimulation (DBS) of the thalamic anterior nuclei (AN) represents a complimentary option for treatment of drug-resistant epilepsies. The putative induction of epileptic seizures by DBS of thalamic AN has been occasionally reported. However, an exact correlation between thalamic stimulation and the electroclinical onset, duration, and semiology of seizures has not been documented until now. Therefore, it is not known whether this side effect occurs as a result of the syndrome and/or protocol. We report the case of a patient with non-lesional epilepsy, who experienced spontaneous and DBS-induced epileptic seizures. In this patient we performed an accurate analysis of the electroclinical effects of thalamic DBS. Methods: A 23 year-old female with non-lesional epilepsy with tonic-dyscognitive focal and bilateral convulsive seizures was treated by means of bilateral deep brain stimulation. DBS electrodes were implanted bilaterally in the thalamic anterior nuclei using a stereotactic technique. The following stimulation parameters were used bilaterally and mostly symmetric: amplitudes between 3 and 7.5 V, frequencies between 145 and 180 Hz, pulse widths between 90 and 120 μs, stimulation cycling on/off between 1min/5min and 20s/20s, stimulation plots: 3 and 11 (most lateral located plots). Results: Immediately after initiation of DBS the patient developed almost stupurous mutism. The electroencephalograms (EEGs) showed series of sharp-slow-waves or high amplitude theta-delta discharges that regularly occurred during the on-phases of a stimulation cycle and correlated well with fluctuating neurocognitive impairments. In a long-term EEG recording, regularly occurring periods of sharp-slow-waves or slow-wave discharges, coincident to the thalamic stimulation were also documented. Neuropsy-chological assessment performed at the end of a stimulation-free period of several months and three days after restarting the thalamic stimulation showed an abrupt impairment of attention and executive functions. Conclusion: In difficult-to-treat epilepsy patients, DBS of the anterior thalamus may occasionally induce electroclinical worsening. P455 Enhanced ictal and interictal gamma coherence in children with idiopathic generalised epilepsy Background and aim: Cortico-thalamo-cortical circuits play a crucial role in generating oscillations in various frequency bands in association with idiopathic generalized epilepsy (IGE). We here tested the hypothesis that cortical rhythmic EEG activity in the gamma band (40-80 Hz) coincided with and possibly caused spike-wave-discharges (SWD) in patients with idiopathic generalised epilepsy (IGE). Method: Ictal and interictal EEG recordings of 14 children with IGE (mean age 8.5±5 years) and age and sex matched controls were evaluated. Network operator functions of high frequency synchronization were assessed in IGE patients during interictal and ictal states with respect to cortical coherence to evaluate cortico-cortical connectivity. Power spectrum density and intra-and inter-hemispheric coherence profiles were estimated using a block autoregressive parametric model.

In a cross-sectional study, we evaluated the impact of the chronic use of benzodiazepines (BDZ) prescribed for seizure control on the anxiety levels of patients with temporal lobe epilepsy. We assessed the anxiety level of 99 patients with temporal lobe epilepsy with (n = 15) or without (n = 84) BDZ for seizure control, using the Beck Anxiety Inventory (BAI) or the Hamilton Anxiety Scale (HAMA). Independent risk factors for high anxiety levels were being a female patient (O.R. = 2.93; 95% C.I. = 1.05–8.16; p = 0.039), having uncontrolled seizures (O.R. = 4.49; 95% C.I. = 1.66–12.11; p = 0.003) and having a history of a psychiatric disorder (O.R. = 4.46; 95% C.I. = 1.63–12.21; p = 0.004). However, there were no statistically significant differences in anxiety levels between patients utilizing or not utilizing BDZ prescribed exclusively for seizure control. We concluded that in our study, patients with chronic use of BDZ prescribed exclusively for seizure control showed similar anxiety levels than patients who were not using this class of drug. Additional studies are needed to define better strategies for the treatment of anxiety disorders in epilepsy.

Objective: To identify independent risk factors for affective disorders in temporal lobe epilepsy. Methods: We studied 97 patients with temporal lobe epilepsy (TLE) exploring variables like age, gender, family history of epilepsy and psychiatric disorders, duration of epilepsy, control of seizures, presence of aura and initial precipitant insult, abuse of substances, neuroimaging and EEG features. Results: Forty-one patients (42.3% of the total population) had affective disorders. A positive family history of psychiatric disorders (O.R. = 3.8; p = 0.003) and interictal EEG epileptiform discharges involving the left temporal lobe (O.R. = 2.9; p = 0.041) were significantly associated with an increased risk for an affective disorder. These associations remained significant after logistic regression, confirming the independent effects of the risk factors observed. Moreover, a binary logistic regression model obtained was able to correctly predict presence or absence of a lifetime affective disorder in 71.1% of patients. Conclusion: This study points out that a positive family history of psychiatric disorders and interictal EEG epileptiform discharges involving the left temporal lobe are isolated risk factors for affective disorders in TLE. Our results suggest that biological factors are crucial for affective disorders development in TLE. Further studies are necessary to better specify the genetic andbr (J.A. Bragatti). J.A. Bragatti et al. anatomical substracts involved and how they come together to generate affective disorders in those patients.