Enhancement of Subjective Quality of Life Following Surgical Intervention in Patients With Drug-Resistant Epilepsy: A Depressive Symptom-Independent Outcome.

PURPOSE: To evaluate the impact of depressive symptoms on the subjective perception of quality of life in patients with drug-resistant epilepsy (DRE) after surgical treatment for seizures.  Methods: A case-control study with DRE patients who received surgical treatment (n=19) and matched non-operated patients (n=23). We assessed the quality of life using the Subjective Handicap of Epilepsy (SHE) scale, alongside measuring depressive symptoms using the Beck Depression Inventory (BDI). RESULTS: The mean age of the participants was 45 years, with females constituting 52.4% of the patients. A majority (73.8%) had been diagnosed with temporal lobe epilepsy. Those who had undergone surgical intervention showed significantly enhanced performance across all quality-of-life domains on the SHE scale independently of depressive symptoms. The domains of "Work and Activity," "Physical Health," and "Self-Perception" displayed the greatest improvements, with the surgical group's averages outperforming the control group by factors of 1.87, 2.53, and 2.81, respectively. Influential differences impacting the quality-of-life scores included seizure frequency, the quantity of antiepileptic drugs utilized, and the incidence of convulsive seizures. CONCLUSION: The findings suggest that surgical control of seizures in drug-resistant focal epilepsy is associated with improvement in quality of life across various domains, independently of the depressive symptoms of the patients.

Single Burr-Hole Extended Transforaminal Approach for Concurrent Endoscopic Surgery in the Third Ventricle Posterior to the Foramen of Monro and Ventriculostomy: Clinical Series and Planning Steps.

OBJECTIVE: For endoscopic surgery of third ventricular lesions posterior to the foramen of Monro that frequently require a third ventriculostomy during the same procedure, the extended transforaminal approach (ETFA) through the choroid fissure has been proposed. This study reports clinical results and provides anatomic background and guidelines for individual planning of a single burr-hole approach and a safe transchoroid entry zone. METHODS: A retrospective review was undertaken of 25 cases of concurrent third ventricle surgery and third ventriculostomy via ETFA. Assessment was made of a safe transchoroidal entry zone on cadavers (6 hemispheres) and of planning guidelines on magnetic resonance imaging showing occlusive hydrocephalus (30 sides). RESULTS: ETFA was feasible in all 25 cases. The safe transchoroid entry zone was sufficient in 16 cases; in 9 cases, additional transchoroid opening with transection of the anterior septal vein was required without clinical consequences. The anatomic study showed a safe transchoroid entry zone of 5 mm (3-6 mm) for posterior enlargement of the foramen of Monro. Individual planning on magnetic resonance imaging of patients with enlarged third ventricles showed an optimal burr-hole position 22 mm (10-30 mm) lateral to the midline and 8 mm (27 to -23 mm) precoronal; a foramen of Monro diameter of 7 mm (3-11 mm) and a safe transchoroid entry zone of 6 mm (3-12 mm). CONCLUSIONS: According to our data, concurrent endoscopic surgery of third ventricular lesions posterior to the foramen of Monro and ventriculostomy are feasible through a single burr hole and a transchoroid extension of the transforaminal approach. Precise preoperative planning is recommended for anticipating the individual anatomic nuances.

The approach to patients with psychogenic nonepileptic seizures in epilepsy surgery centers regarding diagnosis, treatment, and education.

Previous studies, using surveys, provided an understanding about how health-care providers address patients with PNES. To date, there is limited information on the management of patients with PNES by tertiary referral centers for epilepsy. In this study, we surveyed 11 Brazilian epilepsy center directors about diagnosis, treatment, education and research on PNES. Respondents reported that patients with PNES represented 10-20% of all adult patients recorded by video-EEG (VEEG). All respondents recognized VEEG as the method to confirm the diagnosis, and 81.8% used this approach for confirmation. Most centers had a standard protocol for diagnosis. None of the centers had a particular protocol to treat PNES, but 90.9% had a uniform treatment approach including therapy and educational measures. Psychotherapy was not easily obtained in nine centers (81.8%). Seven (63.3%) centers reported ongoing research projects with PNES. Five centers referred to an educational PNES program discussing diagnosis, but only one reported an educational program for treatment. This study showed a commitment to PNES diagnosis; however, some gaps remain regarding treatment and training, namely implementing a psychotherapy approach for patients and providing educational curricula for clinicians.

Neuroimaging observations linking neurocysticercosis and mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: To test if chronic calcificed neurocysticercosis (cNCC) and hippocampal sclerosis occur more often than by chance ipsilateral to the same brain hemisphere or brain region in mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) plus neurocysticercosis. This proof-of-concept would provide important evidence of a direct pathogenic relationship between neurocysticercosis and MTLE-HS. METHODS: A cohort of 290 consecutive MTLE-HS surgical patients was studied. A test of proportions was used to analyze if the proportion of patients with a single cNCC lesion matching the same brain hemisphere or region of hippocampal sclerosis was significantly greater than 50%, as expected by the chance. RESULTS: Neuroimaging findings of cNCC were observed in 112 (38.6%) of 290 MTLE-HS patients and a single cNCC lesion occurred in 58 (51.8%) of them. There were no differences in main basal clinical characteristics of MTLE-HS patients with single or multiple cNCC lesions. In patients with single cNCC lesions, the lesion matched the side in which hippocampal sclerosis was observed in 43 (74.1%) patients, a proportion significantly greater than that expected to occur by chance (p=0.008). Neurocysticercosis in temporal lobe was ipsilateral to hippocampal sclerosis in 85.0% of patients and accounted mostly for this result. CONCLUSIONS: This work is a proof-of-concept that the association of neurocysticercosis and MTLE-HS cannot be explained exclusively by patients sharing common biological or socio-economic predisposing variables. Instead, our results suggest the involvement of more direct pathogenic mechanisms like regional inflammation, repetitive seizures or both. Neurocysticercosis within temporal lobes was particularly related with ipsilateral hippocampal sclerosis in MTLE-HS, a finding adding new contributions for understanding MTLE-HS plus cNCC or perhaps to other forms of dual pathology in MTLE-HS.

Characteristics of mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis.

Recent observations suggest that neurocysticercosis (NCC) might act as an initial precipitating injury (IPI) causing mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). A total of 191 patients from Brazil, a country in which NCC is endemic, were surgically treated for MTLE-HS, and subsequent findings for patients with MTLE-HS were compared with those of patients with MTLE-HS plus NCC. Seventy-one patients (37,2%) presented chronic findings of NCC (cNCC). MTLE-HS plus cNCC was significantly more common in women (O.R.=2.45; 95%CI=1.30-4.60; p=0.005), in patients with no history of classical forms of IPI (O.R.=2.67; 95%CI=1.37-5.18; p=0.004), and in those with bi-temporal interictal spikes on video-EEG (O.R.=2.00; 95%CI=1.07-3.73; p=0.03). Single cNCC lesions were observed to occur significantly more often on the same side as hippocampal sclerosis, a finding suggesting an anatomical relationship between NCC and MTLE-HS. Taken together, our results suggest that NCC may be a marker, or contributes to or even causes MTLE-HS. Based on our findings, we propose two distinct, non-excluding, and potentially synergistic mechanisms involved in the development of MTLE-HS in NCC, one of them being inflammatory-mediated, while the other is electrogenic-mediated. Taken together, our observations may provide further evidence suggesting a role of NCC in the genesis or development of MTLE-HS.

Assessment of Basal Metabolic Rate and Nutritional Status in Patients with Gaucher Disease Type III.

UNLABELLED: Gaucher disease type III (GD III) is a rare form of GD characterized by neurological involvement and severe systemic disease. The objective of this study was to assess the nutritional status and energy metabolism of patients with GD III. METHODS: The basal metabolic rate (BMR, measured by indirect calorimetry) and anthropometric parameters (height, weight, body mass index (BMI), and arm circumference) of three patients with GD III (p.L444P/L444P genotype) were assessed at different time points. The clinical severity of GD was assessed by means of physical examination, laboratory tests, imaging findings, and the severity scores proposed by Zimran (SSI) and Davies (SSNI). RESULTS: The measured BMR of patients 1 (age 14 years, not on enzyme replacement therapy (ERT), SSI score 33, SSNI score 14.5), 2 (age 17 years, on ERT, SSI score 33, SSNI score 16), and 3 (age 20 years, on ERT, SSI score 33, SSNI score 7.5) was, respectively, 47%, 72%, and 15% higher than that estimated by the Harris-Benedict equation. Patients with a more severe phenotype had more marked hypermetabolism. Patients 1 and 2 had BMI-for-age z scores of -1.09 and -1.39, respectively, and height-for-age z scores of -4.27 and -3.02, respectively; patient 3 had a BMI of 24.7 kg/m(2). CONCLUSION: All three patients showed hypermetabolism; however, the two patients with the highest BMR had more severe GD and were malnourished. Additional studies are warranted to assess whether hypermetabolism may be a biomarker of disease severity in GD.

Timing of early and late seizure recurrence after temporal lobe epilepsy surgery.

PURPOSE: Seizure recurrence after epilepsy surgery has been classified as either early or late depending on the recurrence time after operation. However, time of recurrence is variable and has been arbitrarily defined in the literature. We established a mathematical model for discriminating patients with early or late seizure recurrence, and examined differences between these two groups. METHODS: A historical cohort of 247 consecutive patients treated surgically for temporal lobe epilepsy was identified. In patients who recurred, postoperative time until seizure recurrence was examined using an receiver-operating characteristic (ROC) curve to determine the best cutoff for predicting long-term prognosis, dividing patients in those with early and those with late seizure recurrence. We then compared the groups in terms of a number of clinical, electrophysiologic, and radiologic variables. KEY FINDINGS: Seizures recurred in 107 patients (48.9%). The ROC curve demonstrated that 6 months was the ideal time for predicting long-term surgical outcome with best accuracy, (area under the curve [AUC] = 0.761; sensitivity = 78.8%; specificity = 72.1%). We observed that patients with seizure recurrence during the first 6 months started having seizures at younger age (odds ratio [OR] = 6.03; 95% confidence interval [CI] = 1.06-11.01; p = 0.018), had a worse outcome (OR = 6.85; 95% CI = 2.54-18.52; p = 0.001), needed a higher number of antiepileptic medications (OR = 2.07; 95% CI = 1.16-9.34; p = 0.013), and more frequently had repeat surgery (OR = 9.59; 95% CI = 1.18-77.88; p = 0.021). Patients with late relapse more frequently had seizures associated with trigger events (OR = 9.61; 95% CI = 3.52-26.31; p < 0.01). SIGNIFICANCE: Patients with early or late recurrence of seizures have different characteristics that might reflect diversity in the epileptogenic zone and epileptogenicity itself. These disparities might help explain variable patterns of seizure recurrence after epilepsy surgery.

Atypical neuropsychological profiles and cognitive outcome in mesial temporal lobe epilepsy.

Patients with left mesial temporal lobe epilepsy (MTLE) have deficits in verbal memory processes, while patients with right MTLE have visuospatial memory impairment. However, atypical cognitive phenotypes among patients with MTLE may occur. In this study, we analyzed preoperative memory deficits in a cohort of 426 right-handed patients with unilateral MTLE. We also evaluated the cognitive outcome after anterior temporal lobectomy (ATL) of patients with atypical profiles in comparison with those with typical memory profile. We found that 25% of our patients had a typical cognitive profile, with verbal memory deficits associated with left side hippocampal sclerosis (HS) and visuospatial memory deficits associated with right side HS. However, 75% of our patients had atypical memory profiles. Despite these atypical profiles, patients submitted to right ATL had no significant cognitive deficit after surgery. In patients submitted to left ATL, the higher the presurgical scores on verbal memory and naming tests, the higher the cognitive decline after surgery.

Cognitive and surgical outcome in mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis: a cohort study.

BACKGROUND: Where neurocysticercosis (NCC) is endemic, chronic calcified neurocysticercosis (cNCC) can be observed in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). Considering that both disorders cause recurrent seizures or cognitive impairment, we evaluated if temporal lobectomy is cognitively safe and effective for seizure control in MTLE-HS plus cNCC. METHODS: Retrospective cohort study of neuropsychological profile and surgical outcome of 324 MTLE-HS patients submitted to temporal lobectomy, comparing the results according to the presence or absence of cNCC. FINDINGS: cNCC occurred in 126 (38.9%) of our MTLE-HS patients, a frequency higher than expected, more frequently in women than in men (O.R. = 1.66; 95% C.I. = 1.05-2.61; p = 0.03). Left-side (but not right side) surgery caused impairment in selected neuropsychological tests, but this impairment was not accentuated by the presence of cNCC. Ninety-four (74.6%) patients with MTLE-HS plus cNCC and 153 patients (77.3%) with MTLE-HS alone were Engel class I after surgery (O.R. = 1.16; 95% C.I. = 0.69-1.95; p = 0.58). However, the chances of Engel class IA were significantly lower in MTLE-HS plus cNCC than in patients with MTLE-HS alone (31.7% versus 48.5%; O.R. = 2.02; 95% C.I. = 1.27-3.23; p = 0.003). Patients with MTLE-HS plus cNCC showed higher rates of Engel class ID (15.1% versus 6.6%; O.R. = 2.50; 95% C.I. = 1.20-5.32; p = 0.012). INTERPRETATION: cNCC can be highly prevalent among MTLE-HS patients living in areas where neurocysticercosis is endemic, suggesting a cause-effect relationship between the two diseases. cNCC does not add further risk for cognitive decline after surgery in MTLE-HS patients. The rates of Engel class I outcome were very similar for the two groups; however, MTLE-HS plus cNCC patients achieved Engel IA status less frequently, and Engel ID status more frequently. Temporal lobectomy can be safely performed in most patients with MTLE-HS plus cNCC without affecting cognitive outcome. Long-term surgical seizure control in MTLE-HS plus cNCC is still satisfactory, as long as selected patients remain under medication.

Psychiatric comorbidity in refractory focal epilepsy: a study of 490 patients.

We studied the prevalence and associated factors of psychiatric comorbidities in 490 patients with refractory focal epilepsy. Of these, 198 (40.4%) patients had psychiatric comorbidity. An Axis I diagnosis was made in 154 patients (31.4%) and an Axis II diagnosis (personality disorder) in another 44 (8.97%) patients. After logistic regression, positive family history of psychiatric comorbidities (O.R.=1.98; 95% CI=1.10-3.58; p=0.023), the presence of Axis II psychiatric comorbidities (O.R.=3.25; 95% CI=1.70-6.22; p<0.0001), and the epileptogenic zone located in mesial temporal lobe structures (O.R.=1.94; 95% CI=1.25-3.03; p=0.003) remained associated with Axis I psychiatric comorbidities. We concluded that a combination of clinical variables and selected structural abnormalities of the central nervous system contributes to the development of psychiatric comorbidities in patients with focal epilepsy.

Independent predictors and a prognostic model for surgical outcome in refractory frontal lobe epilepsy.

PURPOSE: Refractory frontal lobe epilepsy (FLE) remains one of the most challenging surgically remediable epilepsy syndromes. Nevertheless, definition of independent predictors and predictive models of postsurgical seizure outcome remains poorly explored in FLE. METHODS: We retrospectively analyzed data from 70 consecutive patients with refractory FLE submitted to surgical treatment at our center from July 1994 to December 2006. Univariate results were submitted to logistic regression models and Cox proportional hazards regression to identify isolated risk factors for poor surgical results and to construct predictive models for surgical outcome in FLE. RESULTS: From 70 patients submitted to surgery, 45 patients (64%) had favorable outcome and 37 (47%) became seizure free. Isolated risk factors for poor surgical outcome are expressed in hazard ratio (H.R.) and were time of epilepsy (H.R.=4.2; 95% C.I.=1.5-11.7; p=0.006), ictal EEG recruiting rhythm (H.R.=2.9; 95% C.I.=1.1-7.7; p=0.033); normal MRI (H.R.=4.8; 95% C.I.=1.4-16.6; p=0.012), and MRI with lesion involving eloquent cortex (H.R.=3.8; 95% C.I.=1.2-12.0; p=0.021). Based on these variables and using a logistic regression model we constructed a model that correctly predicted long-term surgical outcome in up to 80% of patients. CONCLUSION: Among independent risk factors for postsurgical seizure outcome, epilepsy duration is a potentially modifiable factor that could impact surgical outcome in FLE. Early diagnosis, presence of an MRI lesion not involving eloquent cortex, and ictal EEG without recruited rhythm independently predicted favorable outcome in this series.

Evidence of association between Val66Met polymorphism at BDNF gene and anxiety disorders in a community sample of children and adolescents.

Different lines of evidence support BDNF as a candidate gene in mood and anxiety modulation. More recently, the Met allele of the BDNF Val66Met polymorphism has been implicated in anxiety in animal models and anxiety-traits in humans. The aim of this study is to evaluate the a priori hypothesis that the association between anxiety disorders and Val66Met polymorphism at the BDNF gene would be replicated in a community sample of children and adolescents. 240 subjects from a total sample of 2457 children and adolescents aged 10-17 years from the public schools in the catchment area of the primary care unit of a university hospital participated in this case-control study and were assessed for psychopathology using the K-SADS-PL. A sample of saliva was collected for DNA analysis of Val66Met polymorphism. BDNF was the single gene evaluated in this sample. We found a significant association between carrying one copy of the Met allele and higher chance of anxiety disorders in children and adolescents. The association remained positive even after the adjustment for potential confounders (228 subjects; OR=3.53 (CI95% 1.77-7.06; p<0.001)). Our results support the a priori hypothesis of an association between anxiety and the polymorphism Val66Met. To our knowledge, this is the first study documenting a potential role of this polymorphism in a community sample of anxious children and adolescents.

Utility of ictal single photon emission computed tomography in mesial temporal lobe epilepsy with hippocampal atrophy: a randomized trial.

BACKGROUND: The development of newer diagnostic technologies has reduced the need for invasive electroencephalographic (EEG) studies in identifying the epileptogenic zone, especially in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). OBJECTIVE: To evaluate ictal single photon emission computed tomography (SPECT) in the evaluation and treatment of patients with MTLE-HS. METHODS: MTLE patients were randomly assigned to those with (SPECT, n = 124) and without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end points were the proportion of patients with invasive EEG studies, and those offered surgery. Secondary end points were the length of hospital stay and the proportion of patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical seizure outcome, and hospital cost. RESULTS: The proportion of patients offered surgery was similar in the SPECT (85%) and non-SPECT groups (81%), as well as the proportion that had invasive EEG studies (27% vs 23%). The mean duration of hospital stay was 1 day longer for the SPECT group (P < 0.001). SGS occurred in 51% of the SPECT and 26% of the non-SPECT group (P < 0.001). The cost of the presurgical evaluation was 35% higher for the SPECT compared with the non-SPECT group (P < 0.001). The proportion of patients seizure-free after surgery was similar in the SPECT (59%) compared with non-SPECT group (54%). CONCLUSION: Ictal-SPECT did not add localizing value beyond what was provided by EEG-video telemetry and structural MRI that altered the surgical decision and outcome for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased costs and a higher chance of SGS during video-EEG monitoring. These findings support the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the presurgical evaluation of adult patients with MTLE-HS.

Correlation between temporal pole MRI abnormalities and surface ictal EEG patterns in patients with unilateral mesial temporal lobe epilepsy.

OBJECTIVE: The objective of this retrospective study is to analyze ictal patterns observed during continuous Video-EEG monitoring in patients with temporal lobe epilepsy (TLE) due to unilateral hippocampal sclerosis (HS), and to correlate these EEG patterns to temporal pole abnormalities observed on magnetic resonance imaging exams. METHODS: We analyzed 147 seizures from 35 patients with TLE and unilateral HS. Ictal patterns were classified and correlated to signal abnormalities and volumetric measures of the temporal poles. Volume differences over 10% were considered abnormal. RESULTS: The most frequent type of ictal pattern was rhythmic theta activity (RTA), encountered in 65.5% of the seizures. Rhythmic beta activity (RBA) was observed in 11% of the seizures, localized attenuation in 8%, interruption of epileptiform discharges in 6%, repetitive discharges in 5.5%, and rhythmic delta activity (RDA) in 4%. Sixty-six percent of the patients presented signal abnormalities in the temporal pole that were always ipsilateral to the HS. Sixty percent presented significant asymmetry of the temporal poles consisting of reduced volume that was also always ipsilateral to HS. Although patients with RTA as the predominant ictal pattern tended to present asymmetry of temporal poles (p=0.305), the ictal EEG pattern did not correlate with temporal pole asymmetry or signal abnormalities. CONCLUSIONS: RTA is the most frequent initial ictal pattern in patients with TLE due to unilateral HS. Temporal pole signal changes and volumetric reduction were commonly found in this group of patients, both abnormalities appearing always ipsilateral to the HS. However, neither temporal pole volume reduction nor signal abnormalities correlated with the predominant ictal pattern, suggesting that the temporal poles are not crucially involved in the process of epileptogenesis.