Giulio N. Meldolesi

Ictal heart rate increase precedes EEG discharge in drug-resistant mesial temporal lobe seizures

OBJECTIVE Heart rate (HR) changes, mainly tachycardia, are often observed during seizures originating from the temporal lobe. The aim of this study was to analyze the role of ictal HR changes in localizing both mesial and lateral temporal lobe epilepsy (TLE) in a group of 68 patients. The influence of the gender and the side of epilepsy on HR modulation was also evaluated. METHODS Ictal HR was recorded during prolonged Video-EEG monitoring performed in 68 patients affected by drug-resistant TLE during a non-invasive pre-surgical protocol. According to the electro-clinical correlation, obtained by video-EEG monitoring, one hundred-thirteen seizures (n=113) and one hundred-forty-four auras (n=144) were identified and included in the study. Furthermore, the electro-clinical correlation allowed the classification of all the epileptic events (seizures and auras) as having mesial or lateral origin, based on the temporal lobe seizure onset zone. Ictal HR was calculated with respect to the R-R waves, and assessed from 15 sec (s) before (T(- 15)) to 15 s after (T(+15)) the time of EEG seizure onset (T(0)). RESULTS We observed a high incidence (92%) of ictal HR increase in TLE seizures. When the ictal EEG indicated a seizure onset from the mesial temporal structures, the onset of ictal HR increase preceded by about 5 s the EEG ictal onset (SD+/-18.4), whereas the onset of HR increase coincided with the onset of EEG discharges (SD+/-14.8) when the ictal EEG indicated the onset of seizures from the lateral temporal structures. No significant differences were found between male and female patients; and between right and left TLE. CONCLUSIONS Our findings show that ictal HR increase, preceding the onset of the EEG discharge, is associated with ictal EEG seizure pattern defining temporal lobe seizures originating from the mesial temporal lobe structures; this association suggests that the HR changes may be coupled to the functional impairment of neural circuits involved in sympathetic cardiovascular regulation, in the mesial temporal lobe structures. Further studies investigating the relationship between intracranial EEG monitoring and ECG recording are worthwhile, to confirm our results and to give further indications on the pathogenesis of ictal HR abnormalities.

Temporal lobe epilepsy surgery: different surgical strategies after a non-invasive diagnostic protocol

Aim: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on “anatomo–electro–clinical correlations”. Methods: All consecutive patients with suspected TLE and seizure history <2 years were entered into the protocol, which included video-electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI). Three different TLE subsyndromes (mesial, lateral, mesiolateral) were identified by combined anatomical, electrical, and clinical criteria. “Tailored” surgery for each subsyndrome was offered. Patients with seizure history <2 years, MRI evidence of temporal mass lesion, and concordant interictal EEG and clinical data bypassed video-EEG monitoring and were directly scheduled for surgery. Results: Lesionectomy was performed without video-EEG recording in 11 patients with tumorous TLE. Of 146 patients studied with video-EEG, 133 received a TLE diagnosis. Four were excluded for neuropsychological risks, eight refused surgery, and 121 underwent surgery. Of 132 consecutive patients who underwent surgery, 101 had at least one year of follow up. They were divided into a “hippocampal sclerosis/cryptogenic” group (n = 57) and a “tumours/cortical organisation disorders” group (n = 44). In the first group, extensive temporal lobectomy (ETL) was performed in 40 patients, anteromesial temporal lobectomy (AMTL) in 17 patients. At follow up, 47 patients were seizure free. In the second group, lesionectomy plus ETL was performed in 23 patients, lesionectomy plus AMTL in six patients, and lesionectomy alone in 15 patients. Thirty nine patients were seizure free. Conclusions: These findings suggest that different TLE subsyndromes can be identified accurately using non-invasive anatomo–electro–clinical data and can be treated effectively and safely with tailored surgery.

Seizure clusters and adverse events during pre-surgical video-EEG monitoring with a slow anti-epileptic drug (AED) taper

OBJECTIVE To evaluate the efficiency and safety of pre-surgical video-EEG monitoring with a slow anti-epileptic drug (AED) taper and a rescue benzodiazepine protocol. METHODS Fifty-four consecutive patients with refractory focal epilepsy who underwent pre-surgical video-electroencephalography (EEG) monitoring during the year 2010 were included in the study. Time to first seizure, duration of monitoring, incidence of 4-h and 24-h seizure clustering, secondarily generalised tonic-clonic seizures (sGTCS), status epilepticus, falls and cardiac asystole were evaluated. RESULTS A total of 190 seizures were recorded. Six (11%) patients had 4-h clusters and 21 (39%) patients had 24-h clusters. While 15 sGTCS were recorded in 14 patients (26%), status epilepticus did not occur and no seizure was complicated with cardiac asystole. Epileptic falls with no significant injuries occurred in three patients. The mean time to first seizure was 3.3days and the time to conclude video-EEG monitoring averaged 6days. CONCLUSION Seizure clustering was common during pre-surgical video-EEG monitoring, although serious adverse events were rare with a slow AED tapering and a rescue benzodiazepine protocol. SIGNIFICANCE Slow AED taper pre-surgical video-EEG monitoring is fairly safe when performed in a highly specialised and supervised hospital setting.

Memory outcome 2 years after anterior temporal lobectomy in patients with drug-resistant epilepsy

PURPOSE Memory decline is often observed after anterior temporal lobectomy (ATL), particularly in patients with dominant hemisphere resections. However, the follow-up length has been 1 year or less in most studies. Our aims were to examine postoperative memory changes over a longer period and to identify baseline demographic and clinical predictors of memory outcome. METHODS We administered material-specific memory tests at baseline, and 1 and 2 years after surgery to 82 consecutive right-handed patients (52% males) who underwent ATL for drug-resistant temporal lobe epilepsy (TLE) (35 left, 47 right) after a non-invasive presurgical protocol. Repeated measures multivariate analysis of variance (RM-MANOVA) was used to examine the relationship between changes in memory tests scores over time and side of TLE and pathology. Also, standardized residual change scores were calculated for each memory test and entered in multiple linear regression models aimed at identifying baseline predictors of better memory outcome. RESULTS RM-MANOVA revealed a significant change in memory test scores over time, with an interaction between time and side of surgery, as 2 years after surgery patients with RTLE were improved while patients with LTLE were not worse as compared with baseline. Pathology was not associated with changes in memory scores. In multiple regression analysis, significant associations were found between right TLE and greater improvement in verbal memory, younger age and greater improvement in visuospatial memory, and male gender and greater improvement in both verbal and visuospatial memory. CONCLUSIONS Our results suggest that the long-term memory outcome of TLE patients undergoing ATL without invasive presurgical assessment may be good in most cases not only for right-sided but also for left-sided resections.

Severe amnesia following bilateral medial temporal lobe damage occurring on two distinct occasions.

A comprehensive neuropsychological assessment was performed on a 38-year-old woman with drug-resistant right temporal lobe epilepsy before temporal lobectomy, during a 2-year follow-up period, and approximately 3 years after surgery when she developed a malignant glioma in the left medial temporal lobe (MTL). Both before and after epilepsy surgery, memory function was normal. When the tumour was discovered, the patient suffered from severe retrograde and anterograde amnesia, whereas working memory and the other cognitive abilities were preserved. Compared with other cases of bilateral temporal lesion, this case is peculiar because the damage occurred on two distinct occasions. It suggests that only one MTL can allow normal memory function, or can take over the function normally subserved by a dysfunctional contralateral MTL when the dysfunction is marked and prolonged, such as in chronic epilepsy.

Lateralizing value of memory tests in drug-resistant temporal lobe epilepsy

Our aim was to test the lateralizing value of a neuropsychological battery including several memory tests on a large sample of consecutive patients with drug‐resistant temporal lobe epilepsy (TLE) evaluated for epilepsy surgery. We studied 73 right‐handed patients (56% males, mean age 35.3 ± 11.2 years, 49% left TLE) aged 16 years or older with normal IQ who underwent a preoperative neuropsychological assessment including several memory tests and were seizure‐free after at least 1 year of follow‐up. Forty‐seven had TLE due to hippocampal sclerosis, whilst 26 had TLE secondary to tumors or other lesions. Receiver Operating Characteristic (ROC) analysis and discriminant function analysis were used to evaluate the lateralization value of selected tests and of the battery as a whole, respectively. In patients with TLE secondary to tumors or other lesions, no test showed significant lateralizing value. In patients with TLE due to hippocampal sclerosis, the immediate (P < 0.01) and delayed (P < 0.001) Rey Auditory Verbal Learning Test (RAVLT) displayed substantial discriminatory ability. The battery as a whole correctly classified 82% of patients with respect to side of epileptogenesis. Our findings suggest that a non‐invasive, relatively short and unexpensive neuropsychological battery based on memory tests may profitably complement other well‐established diagnostic procedures such as video‐EEG or magnetic resonance imaging (MRI), at least in patients with drug‐resistant TLE due to hippocampal sclerosis.

Genital and sexual manifestations in drug-resistant partial epilepsy

Genital and sexual manifestations represent rare clinical phenomena during or after focal seizures. The semiology of these types of automatisms is controversial. In particular, it is unclear whether temporal or frontal structures are involved in their generation and whether these clinical manifestations have a potential lateralizing value. In this view, from a population of 212 consecutive patients with drug resistant focal epilepsy referred to us for presurgical assessment, we retrospectively identified 24 patients with genital ictal manifestations. We evaluated the incidence of these behaviours, the clinical semiology, the associated symptoms/signs with the corresponding ictal EEG findings and their potential role in lateralizing the epileptogenic zone. Our results indicate that ictal genital automatisms are possible in seizures originating from temporal lobe and they cannot be attributed exclusively to frontal lobe seizures. In particular, the most frequent genital automatisms consist in subtle phenomena while hypermotoric behaviour, such as pelvic rhythmic movements are quite rare. No lateralizing value for genital automatisms was disclosed.

Attachment and parenting in adult patients with anxiety disorders.

Background: The literature suggests that dysfunctional parenting and insecure attachment may increase risk of anxiety-related psychopathology. This study aimed at testing the association between anxiety disorders, attachment insecurity and dysfunctional parenting while controlling for factors usually not controlled for in previous studies, such as gender, age, and being ill. Methods: A sample of 32 non-psychotic inpatients with SCID-I diagnosis of an anxiety disorder, either alone or in comorbidity, was compared with two age- and sex-matched control groups consisting of 32 non-clinical participants and 32 in-patients with drug-resistant epilepsy. Study measures included the Experience in Close Relationships questionnaire (ECR) and the Parental Bonding Instrument (PBI). Results: The patients with anxiety disorders scored significantly higher on attachment-related anxiety and avoidance than patients with drug-resistant epilepsy and non-clinical participants. These findings were independent of comorbidity for mood disorders. ECR scores did not differ among diagnostic subgroups (generalized anxiety disorder, panic disorder, other anxiety disorders). Patients with anxiety disorders scored significantly lower on PBI mother’s care and borderline significantly lower on PBI fathers care than patients with drug-resistant epilepsy. Conclusions: Although limitations such as the relatively small sample size and the cross-sectional nature suggest caution in interpreting these findings, they are consistent with the few previous adult studies performed on this topic and corroborate Bowlbys seminal hypothesis of a link between negative attachment-related experiences, attachment insecurity, and clinical anxiety. Attachment theory provides a useful theoretical framework for integrating research findings from several fields concerning the development of anxiety disorders and for planning therapeutic interventions.

Prognostic significance of acute postoperative seizures in extra-temporal lobe epilepsy surgery

OBJECTIVE This study aims to assess the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy. METHODS We studied 77 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2 years (mean duration of follow-up 6.2 years, range 2-14). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class I at the last contact were classified as having a favourable outcome. RESULTS Seizure outcome was favourable in 47 patients (61%). The occurrence of APOS and incompleteness of resection were found to be independently associated with unfavourable outcome in a multiple regression model including all preoperative factors identified as outcome predictors in univariate analysis. Duration of illness was the only independent preoperative predictor of APOS. CONCLUSIONS Our study suggests that APOS may predict long-term outcome in patients undergoing resective surgery for ET epilepsy. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicentre studies. SIGNIFICANCE Caution may be required in the clinical management of patients experiencing APOS.

Partial seizures due to sclerosis of the right amygdala presenting as panic disorder. On the importance of psychopathological assessment in differential diagnosis.

The differential diagnosis between panic disorder and focal epilepsy may sometimes pose a serious challenge. We report the case of a 32-year-old woman who complained of paroxysmal episodes of acute anxiety that evaded diagnosis for 8 years. Standard EEGs and brain CT scan showed no clear pathologic findings. Antidepressants, support psychotherapy and several courses of antiepileptic drugs were not beneficial. She was referred to our centre for a comprehensive diagnostic assessment. Clinical and standardized personality assessment did not reveal the personality organization typically associated with proneness to develop phobic anxiety disorders. Also, agoraphobic avoidance was absent, and the patient’s main worries during the episodes involved negative social judgments rather than health. A brain MRI revealed a slightly increased signal at FLAIR images in the right amygdala. Video-EEG monitoring was decisive in establishing the diagnosis of drug-resistant right mesial temporal lobe epilepsy. Anteromesial temporal lobectomy was offered and successfully performed. Pathological examination of removed brain tissue revealed amygdalar sclerosis and mild hippocampal neuronal loss. At a 6-month follow-up visit, the paroxysmal episodes had completely disappeared. Depression, anxiety and quality of life were markedly improved. This case suggests that focal epilepsy should be considered in patients with paroxysmal episodes of anxiety, especially if dissociative symptoms and atypical clinical features for panic disorder are present, and if there is no satisfactory response to adequate trials of medication and psychotherapy within one year. A careful psychopathological analysis rather than a descriptive enumeration of symptoms is needed to bring these features to light. In such cases, even if routine EEGs or MRI are inconclusive and there is no response to antiepileptic drugs, it would be advisable to perform video-EEG monitoring to rule out partial seizures.