José Augusto Bragatti

Prevalence of psychiatric comorbidities in temporal lobe epilepsy: the value of structured psychiatric interviews

BackgroundAlthough many studies have demonstrated a high prevalence of psychiatric disorders in epileptic patients, most have used unstructured psychiatric interviews for diagnosis, which may lead to significant differences in results. Here we present a study evaluating the prevalence of major psychiatric comorbidities in a cohort of South Brazilian patients with temporal lobe epilepsy using a structured clinical interview.MethodsNeuropsychiatric symptoms were analyzed in 98 patients (39 men and 59 women) with temporal lobe epilepsy. Patient mean age was 43 years old, and mean duration of epilepsy was 25 years. Patients were diagnosed according to the ILAE Classification of Epileptic Syndromes using clinical, EEG, and neuroimaging criteria. All patients participated in the Structured Clinical Interview for DSM-IV (SCID).ResultsFifty-three patients (54.1%) presented major psychiatric comorbidities. Mood disorders were observed in 42 patients (42.9%), the most common being neuropsychiatric disorders. Anxiety disorders were the second most frequent disorders, observed in 18 patients (18.4%). Psychotic disorders and substance abuse were each observed in six patients (6.1%). There were no clinical variables regarding epilepsy characteristics (age of onset, duration, response to antiepileptic drugs) and no MRI features associated with psychiatric disorders. A seven-fold increased risk of mood disorders was identified in patients with inter-ictal EEG abnormalities associated with the left hemisphere.ConclusionRelative to previous reports, we identify a high prevalence of psychiatric disorders in TLE patients, although our data is similar to that observed in other studies which have used similar structured interviews in populations of epileptic patients attending tertiary centres. The wide variation in percentages is probably attributable to the different patient groups investigated and to the even greater variety of diagnostic methods. Structured psychiatric interviews may contribute to a better evaluation of the true prevalence of psychiatric comorbidities in temporal lobe epilepsy.

Serotonin gene polymorphisms and psychiatry comorbidities in temporal lobe epilepsy

OBJECTIVE Neuropsychiatric comorbidities are frequent in temporal lobe epilepsy (TLE). It is biologically plausible that alterations in serotonin-related genes may be involved in higher susceptibility to psychiatric disease in these individuals. Here we report results of an association study of serotonin gene polymorphisms and psychiatry comorbidities in TLE. METHODS Case-control study of 155 patients with temporal lobe epilepsy. We evaluate the influence of 5-HTTLPR and 5-HTTVNTR polymorphisms in the 5-HTT gene and the C-1019G polymorphism in the 5-HT1A gene in psychiatric comorbidities of TLE. RESULTS After logistic regression, female sex (OR=2.34; 95% CI 1.06-5.17; p=0.035) and the presence of C allele of 5-HT1A C-1019G polymorphism (OR=2.77; 95% CI 1.01-7.63; p=0.048) remained independent risk factors for anxiety disorders in temporal lobe epilepsy. CONCLUSION C allele of 5-HT1A C-1019G polymorphism might be an independent risk factor for anxiety disorders in temporal lobe epilepsy. We believe that other studies in this venue will shade some light on molecular mechanisms involved in psychiatric comorbidities in epilepsy.

Musical hallucinations following insular glioma resection

Hallucinations can be auditory, visual, tactile, gustatory, or olfactory, and can be caused by psychiatric (such as schizophrenia and depression), neurological (such as cerebrovascular accidents, neoplasia, and infection), or endocrine and metabolic disorders. Musical hallucinations related to neurological disorders are rare. The authors present a case of a patient with a right insular glioma who developed transient musical hallucinations after microsurgical resection of the tumor.

Serotonin transporter gene (5HTT) polymorphisms and temporal lobe epilepsy.

OBJECTIVE Preclinical and clinical studies have shown that serotonin levels might modulate susceptibility to seizures. Here we evaluated an association between 5HTTLPR and 5HTTVNTR allele variants in serotonin transporter gene and epileptogenesis in temporal lobe epilepsy (TLE). METHODS A case-control candidate gene study evaluating the frequencies of 5HTTLPR biallelic and 5HTTVNTR allele variants in patients and healthy subjects. Genotypes were grouped according to transcriptional efficiency. Cases were 175 patients with TLE selected from the Epilepsy Outpatient Clinic of Hospital de Clínicas de Porto Alegre, classified according to the electroclinical classification of the ILAE and neuroimaging findings. The control group consisted of 155 healthy unrelated subjects selected from the same population. RESULTS We observed that less efficient transcriptional genotypes for 5-HTT polymorphisms were more frequent in epileptic patients (O.R.=3.24; 95% C.I.=1.08-9.73; p=0.036). Our results suggest that less efficient transcriptional genotypes for serotonin transporter gene are associated with TLE. CONCLUSION In this study we observed an association between the presence of 5HTTLPR and 5-HTTVNTR less transcriptional efficient combined genotypes and TLE. Our results suggest that modulation of the serotoninergic system might be implied in epileptogenesis in TLE.

Prevalence of psychiatric comorbidities in temporal lobe epilepsy in a Southern Brazilian population

A great prevalence of psychiatric disorders in epilepsy is well demonstrated, although most studies have used unstructured psychiatric interviews for diagnosis. Here we present a study evaluating the prevalence of psychiatric comorbidities in a cohort of Southern Brazilian patients with temporal lobe epilepsy (TLE) using a structured clinical interview. We analyzed 166 patients with TLE regarding neuropsychiatric symptoms through the Structured Clinical Interview for DSM-IV. One hundred-six patients (63.9%) presented psychiatric comorbidities. Mood disorders were observed in 80 patients (48.2%), anxiety disorders in 51 patients (30.7%), psychotic disorders in 14 (8.4%), and substance abuse in 8 patients (4.8%) respectively. Our results agree with literature data where most authors detected mental disorders in 10 to 60% of epileptic patients. This wide variation is probably attributable to different patient groups investigated and to the great variety of diagnostic methods. Structured psychiatric interviews might contribute to a better evaluation of prevalence of psychiatric comorbidities in TLE.

Proteus syndrome associated with hemimegalencephaly and Ohtahara syndrome: Report of two cases

The authors report two cases of Brazilian children with most of the common syndromic features of Proteus syndrome, such as asymmetric overgrowth of tissues, skin abnormalities, hypotonia and mental retardation. In both patients, a refractory epilepsy, compatible with Ohtahara syndrome, as well as hemimegalencephaly, with asymmetric distribution of facial fat, were also diagnosed.

Tryptophan hydroxylase 2 (TPH2) gene polymorphisms and psychiatric comorbidities in temporal lobe epilepsy

Psychiatric comorbidities are frequent in temporal lobe epilepsy (TLE). It is plausible that variance in serotonin-related genes is involved in the susceptibility of these associations. We report here the results on the association of tryptophan hydroxylase 2 (TPH2) gene polymorphisms with psychiatric comorbidities in TLE. A cohort study was conducted on 163 patients with TLE. We assessed the influence of the rs4570625 and rs17110747 polymorphisms in the TPH2 gene on psychiatric comorbidities in TLE. In patients with TLE, the presence of the T allele in the rs4570625 polymorphism was associated with psychotic disorders (OR=6.28; 95% CI=1.27-17.54; p=0.02), while the presence of the A allele in the rs17110747 polymorphism was associated with alcohol abuse (OR=20.33; 95% CI=1.60-258.46; p=0.02). Moreover, we identified male gender (OR=11.24; 95% CI=1.68-76.92; p=0.01) and family history of psychiatric disorder (OR=15.87; 95% CI=2.46-100; p=0.004) as factors also associated with alcohol abuse in TLE. Conversely, a family history of epilepsy was inversely associated with alcohol abuse (OR=0.03; 95% CI=0.001-0.60; p=0.02). Tryptophan hydroxylase 2 gene allele variants might be risk factors for psychiatric conditions in TLE. More specifically, we observed that the T allele in the rs4570625 polymorphism was associated with psychotic disorders, and the A allele in the rs17110747 TPH2 polymorphism was associated with alcohol abuse in patients with TLE. We believe that this study may open new research venues on the influence of the serotonergic system associated with psychiatric comorbidities in epilepsy.

Left-sided EEG focus and positive psychiatric family history are independent risk factors for affective disorders in temporal lobe 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 life-time 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 and anatomical substracts involved and how they come together to generate affective disorders in those patients.

No major clinical impact of Val66Met BDNF gene polymorphism on temporal lobe epilepsy

OBJECTIVE To report the frequencies of Val66Met polymorphism in patients with temporal lobe epilepsy (TLE) compared to normal controls. We also investigated whether Val66Met promoted differences in major clinical variables of TLE. METHODS A case-control study comparing the frequencies of Val66Met polymorphism in 101 Caucasian TLE patients and in 104 Caucasian normal matching controls. In the second step, we evaluated the patient group in terms of the major clinical and electrographic variables related to the epileptogenic process. RESULTS The frequency of Val66Met polymorphism did not differ between epileptic patients and normal controls. Moreover, the Val66Met polymorphisms did not influence age of epilepsy onset, duration of epilepsy, control of seizures, or extension of the irritative zone. Also, the groups did not differ in terms of family history of epilepsy and presence of aura. CONCLUSION In spite of abundant evidence that Val66Met BDNF polymorphism has an impact on several different neurological or psychiatric disorders, we conclude that a major clinical impact of Val66Met polymorphism as a disease modifier in temporal lobe epilepsy is probably unlikely.

Psychiatric Comorbidities of Epilepsy: A Review

People with epilepsy (PWE) have an increased risk for cognitive, behavioral, and psychosocial disorders. The presence of comorbidities may directly affect quality of life of PWE. For example, there is an increased risk for suicide in PWE, compared to the general population. Association between epilepsy and mental disorders is a condition known since Antiquity, and its ranges from 20 to 50%, reaching 80% in selected populations, like individuals with temporal lobe epilepsy (TLE), and medically intractable patients, candidates to surgical treatment, and these indices are far superior to those found in general population (10-20%). Risk factors for the main psychiatric comorbidities in PWE (depression, anxiety and psychosis) are classified in (1) neurobiological, (2) psychosocial, and (3) pharmacological factors. There is a bidirectional relationship between epilepsy and mental disorders, namely, not only the epileptic disorder can antedate settlement of psychiatric symptoms in a given patient, but also the diagnosis of mood and behavioral disorders may be made before a first epileptic seizure. This bidirectionality suggests that structural and functional modifications of one disease increase the risk for the development of the other. In this review, we included the most recent articles concerning the terms “mental disorders”, “epilepsy”, and “risk factors” in PubMed. Book chapters were also referred for this work. We gave preference for population-based studies, especially those with more than 100 patients studied.