Hippocampal sclerosis is associated with celiac disease type immunity in patients with drug-resistant temporal lobe epilepsy.

BACKGROUND: A prior small-scale single center study suggested an association between celiac disease (CD)-type immunity and refractory temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). The present study addresses this putative association in a large, well-characterized group of drug-resistant epilepsy (DRE) patients. These patients were grouped based on the spectrum of CD and gluten sensitivity-associated antibodies. METHODS: In this cross-sectional study, 253 consecutive adult epilepsy patients (135 females, 118 males; age 16-76 years) were categorized into three groups: (i) CD-positive group with either prior diagnosis of CD or CD-specific TG2/EmA antibodies, (ii) AGA-positive group with antigliadin antibodies (AGA) but without CD, and (iii) CD/AGA-negative group without any gluten sensitivity-associated antibodies or CD. Clinical and immunological findings were then compared among the groups. RESULTS: TLE with HS was more common in the CD-positive group compared to CD/AGA-negative group (31.8% versus 11.9%, P = 0.019). Autoimmune disorders were more common in the AGA-positive group than in the CD/AGA-negative group (P = 0.025). Considering HS lateralization; left lateralization was more common in CD-positive group compared to CD/AGA-negative group (71.4% versus 25%, P = 0.030). TG6 seropositivity did not differ among the groups (P > 0.05). CONCLUSIONS: This study provides further evidence linking TLE with HS and CD-type autoimmunity suggesting that CD-type immune response to gluten can be one potential mechanism as a disease modifier leading to DRE and HS. Understanding these immunological factors is imperative for developing immunomodulatory or dietary treatments for DRE potentially preventing HS progression.

Digital solution in the follow-up of early breast cancer a randomized study.

BACKGROUND: After primary treatment, patients with early breast cancer (EBC) are followed-up for at least 5 years. At the Helsinki University Hospital (HUS) surveillance includes appointments at 1, 3 and 5 years, and between pre-planned visits a phone call service operated by a nurse practitioner for counseling about symptoms related to side-effects or potential recurrence. In 2015 HUS launched a digital solution for cancer patients. This study was designed to find out patient preference, Health related (HR) quality of life (QOL) and satisfaction with a digital solution compared to a phone call service during the first year of follow-up. MATERIAL AND METHODS: Patients with EBC were randomized at the final visit of radiotherapy to surveillance by phone calls or by the digital Noona solution during the first year outside pre-planned visits. After six months the groups were crossed over to the other arm. Primary endpoint was patient preference for either follow-up method among those who had contacted the study nurse at least once by both phone service and digital solution. RESULTS: Out of the 765 patients randomized, 142 had contacted the hospital with both methods and were eligible for inclusion in the analyses of the present study. Out of the 142 patients, 56 preferred phone calls, 43 the digital solution while 43 considered both modalities equal. Preference for the digital solution was higher among patients aged 65 or less. There were no differences in HR QoL or overall satisfaction between the modalities. However, the patients rated the timeliness of response better while using the digital solution. CONCLUSION: Of the patients 30% preferred the digital solution, 40% phone calls while 30% found them equal as the primary follow-up method for EBC during the first year outside pre-planned visits. There is a need to include also digital solutions in surveillance of EBC. CLINICALTRIALS.GOV IDENTIFIER: NCT04980989.

Elevated IL-6 plasma levels are associated with GAD antibodies-associated autoimmune epilepsy.

Background: Antibodies against glutamic acid decarboxylase (GADA) are present in multiple neurological manifestations, such as stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and epilepsy. Increasing data support the clinical significance of GADA as an autoimmune etiology of epilepsy, however, there is not yet definitive evidence to confirm the pathogenic link between GADA and epilepsy. Objective: Interleukin-6 (IL-6), a pro-convulsive and neurotoxic cytokine, and interleukin-10 (IL-10), an anti-inflammatory and neuroprotective cytokine, are crucial inflammatory mediators in the brain. Increased production of IL-6 and its association with epileptic disease profiles are well established, suggesting the presence of chronic systemic inflammation in epilepsy. Therefore, in this study, we investigated the association of plasma cytokine concentrations of IL-6 and IL-10 and their ratio with GADA in patients with drug-resistant epilepsy. Methods: Interleukin-6 and IL-10 concentrations were measured by ELISA in plasma, and the IL-6/IL-10 ratio was calculated in a cross-sectional cohort of 247 patients with epilepsy who had their GADA titers measured previously for their clinical significance in epilepsy. Based on GADA titers, patients were grouped as GADA negative (n = 238), GADA low positive (antibody titers < 1,000 RU/mL, n = 5), and GADA high positive (antibody titers ≥ 1,000 RU/mL, n = 4). Results: Median IL-6 concentrations were significantly higher in patients with high GADA positivity [2.86 pg/mL, interquartile range (IQR) = 1.90-5.34 pg/mL] than in GADA-negative patients [1.18 pg/mL, interquartile range (IQR) = 0.54-2.32 pg/mL; p = 0.039]. Similarly, IL-10 concentrations were also higher in GADA high-positive patients [1.45 pg/mL, interquartile range (IQR) = 0.53-14.32 pg/mL] than in GADA-negative patients [0.50 pg/mL, interquartile range (IQR) = 0.24-1.00 pg/mL], however, the difference was not statistically significant (p = 0.110). Neither IL-6 nor IL-10 concentrations were different between GADA-negative and GADA low-positive patients (p > 0.05) or between GADA low-positive or GADA high-positive patients (p > 0.05). The IL-6/IL-10 ratio was also similar among all the study groups. Conclusion: Increased circulatory concentrations of IL-6 are associated with high GADA titers in patients with epilepsy. These data provide additional pathophysiological significance of IL-6 and help to further describe the immune mechanisms involved in the pathogenesis of GADA-associated autoimmune epilepsy.

Routine and sleep EEG: Minimum recording standards of the International Federation of Clinical Neurophysiology and the International League Against Epilepsy.

This article provides recommendations on the minimum standards for recording routine ("standard") and sleep electroencephalography (EEG). The joint working group of the International Federation of Clinical Neurophysiology (IFCN) and the International League Against Epilepsy (ILAE) developed the standards according to the methodology suggested for epilepsy-related clinical practice guidelines by the Epilepsy Guidelines Working Group. We reviewed the published evidence using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of evidence for sleep induction methods was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. A tool for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias in technical and methodological studies. Where high-quality published evidence was lacking, we used modified Delphi technique to reach expert consensus. The GRADE system was used to formulate the recommendations. The quality of evidence was low or moderate. We formulated 16 consensus-based recommendations for minimum standards for recording routine and sleep EEG. The recommendations comprise the following aspects: indications, technical standards, recording duration, sleep induction, and provocative methods.

Routine and sleep EEG: Minimum recording standards of the International Federation of Clinical Neurophysiology and the International League Against Epilepsy.

This article provides recommendations on the minimum standards for recording routine ("standard") and sleep electroencephalography (EEG). The joint working group of the International Federation of Clinical Neurophysiology (IFCN) and the International League Against Epilepsy (ILAE) developed the standards according to the methodology suggested for epilepsy-related clinical practice guidelines by the Epilepsy Guidelines Working Group. We reviewed the published evidence using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of evidence for sleep induction methods was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. A tool for Quality Assessment of Diagnostic Studies (QUADAS-2) was used to assess the risk of bias in technical and methodological studies. Where high-quality published evidence was lacking, we used modified Delphi technique to reach expert consensus. The GRADE system was used to formulate the recommendations. The quality of evidence was low or moderate. We formulated 16 consensus-based recommendations for minimum standards for recording routine and sleep EEG. The recommendations comprise the following aspects: indications, technical standards, recording duration, sleep induction, and provocative methods.

A Novel Digital Patient-Reported Outcome Platform (Noona) for Clinical Use in Patients With Cancer: Pilot Study Assessing Suitability.

BACKGROUND: As the incidence of cancer is on the rise, there is a need to develop modern communication tools between patients and the medical personnel. Electronic patient-reported outcome (ePRO) measures increase the safety of cancer treatments and may have an impact on treatment outcome as well. ePRO may also provide a cost-efficient way to organize follow-up for patients with cancer. Noona is an internet-based system for patients to self-report symptoms and adverse events of cancer treatments from home via a computer or a smart device (eg, smartphone, tablet). OBJECTIVE: In this pilot study, we assessed the suitability of a novel ePRO application (Noona) for patients with cancer, nurses, and doctors at the Helsinki University Hospital, Finland. METHODS: The study included 44 patients with cancer (different solid tumor types) and 17 health care professionals (nurses or medical doctors). Patients were either operated or received systemic treatment or radiotherapy. Patients reported their symptoms to the medical staff via Noona. In addition, patients and clinicians answered a questionnaire, based on which Noona's suitability for clinical use was evaluated in terms of usability (ease of use, operability, and learnability), reliability (subjective opinion of the participant), and incidence of harmful events reported by the participants. RESULTS: A total of 41/44 (93%) patients and 15/17 (88%) professionals reported that the program was easy or quite easy to use; 38/44 (86%) patients and 11/17 (65%) professionals found Noona reliable, and 38/44 (86%) patients and 10/17 (59%) professionals would recommend Noona to other patients or their colleagues. No harmful incidences caused by the use of Noona were reported by the patients; however, 1 harmful incidence was reported by one of the professionals. CONCLUSIONS: The majority of the participants felt that Noona appeared reliable and it was easy to use. Noona seems to be a useful tool for monitoring patient's symptoms during cancer therapy. Future studies will determine the impact of this ePRO platform in routine clinical practice.

Detrended fluctuation analysis in the presurgical evaluation of parietal lobe epilepsy patients.

OBJECTIVE: To examine the usability of long-range temporal correlations (LRTCs) in non-invasive localization of the epileptogenic zone (EZ) in refractory parietal lobe epilepsy (RPLE) patients. METHODS: We analyzed 10 RPLE patients who had presurgical MEG and underwent epilepsy surgery. We quantified LRTCs with detrended fluctuation analysis (DFA) at four frequency bands for 200 cortical regions estimated using individual source models. We correlated individually the DFA maps to the distance from the resection area and from cortical locations of interictal epileptiform discharges (IEDs). Additionally, three clinical experts inspected the DFA maps to visually assess the most likely EZ locations. RESULTS: The DFA maps correlated with the distance to resection area in patients with type II focal cortical dysplasia (FCD) (p<0.05), but not in other etiologies. Similarly, the DFA maps correlated with the IED locations only in the FCD II patients. Visual analysis of the DFA maps showed high interobserver agreement and accuracy in FCD patients in assigning the affected hemisphere and lobe. CONCLUSIONS: Aberrant LRTCs correlate with the resection areas and IED locations. SIGNIFICANCE: This methodological pilot study demonstrates the feasibility of approximating cortical LRTCs from MEG that may aid in the EZ localization and provide new non-invasive insight into the presurgical evaluation of epilepsy.

Chronically reduced IL-10 plasma levels are associated with hippocampal sclerosis in temporal lobe epilepsy patients.

BACKGROUND: Increasing evidence supports the role of soluble inflammatory mediators in the pathogenesis of refractory temporal lobe epilepsy (TLE). Hippocampal sclerosis (HS) is a well-described pathohistological abnormality in TLE. The association of proinflammatory cytokines with epileptic disease profiles is well established; however, the potential significance of circulating interleukin 10 (IL-10), particularly in TLE-associated HS, is still poorly understood. Therefore, taking into consideration the neuroprotective and anticonvulsive effects of IL-10, we performed this study to examine the role of the plasma levels of IL-10 in patients with TLE with HS (TLE + HS), TLE without HS (TLE-HS) and with other types of epilepsy. METHODS: This study included 270 patients with refractory epilepsy who were classified into four groups: i) 34 patients with TLE + HS, ii) 105 patients with TLE-HS, iii) 95 patients with extra-TLE (XLE) and iv) 36 patients with idiopathic generalized epilepsy (IGE). The plasma IL-10 levels were quantified using a commercially available enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-10 levels were significantly lower in TLE + HS than in TLE-HS (p = 0.013). In a subgroup of TLE-HS patients who had seizures 1 month before sampling, patients with seizures had significantly higher IL-10 levels than patients who were seizure-free (p = 0.039). Among a small group (n = 15) of non-refractory TLE-HS patients, IL-10 levels showed a moderate negative correlation with the duration of epilepsy (r = - 0.585, p = 0.023). CONCLUSIONS: This study demonstrated that chronically reduced levels of plasma IL-10 were associated with HS in TLE patients, suggesting that there was an inadequate systemic anti-inflammatory immune response. These results could provide new biological insights into the pathophysiology of HS in TLE. We also found that the production of IL-10 could be affected by the seizure frequency and declined concomitantly with increased disease durations. Therefore, the measurement of plasma IL-10 may have diagnostic value as a biomarker for stratifying TLE + HS from other epilepsy types or as a marker of disease progression towards a progressive form of epilepsy.

Anatomoelectroclinical features of SEEG-confirmed pure insular-onset epilepsy.

PURPOSE: In this study, we aimed to improve our knowledge of insular epilepsy by studying anatomoelectroclinical correlations in pure insular-onset epilepsy and characterizing differences between anterior and posterior insular-onset seizures. METHODS: Patients in whom seizure-onset zone was confined to the insula and peri-insular sulcus were selected from 301 consecutive presurgical stereo-electroencephalography (EEG) recordings performed between years 2010 and 2017 in two epilepsy centers. Ictal-onset zone in stereo-EEG was delineated visually and quantitatively using epileptogenic index method. Seizure characteristics were reanalyzed, and anatomoelectroclinical correlations were assessed. Characteristics of posterior and anterior insular-onset seizures were compared. RESULTS: Eleven insular cases were identified, five of them with an anterior insular seizure onset and six with a posterior one. Nonpainful somatosensory symptoms and autonomic symptoms were the most common symptoms (73% of patients) followed by speech-related symptoms (55%) and ipsilateral eye blinking (45%). Six patients had seizures restricted to somatosensory or viscerosensory symptoms. In all patients, seizures progressed to motor symptoms. Somatosensory symptoms did not differentiate anterior from posterior insular seizures. However, hyperkinetic signs, speech modifications, and viscerosensory symptoms were related to an anterior insular seizure-onset zone. Pain, asymmetric tonic, focal clonic, and tonic symptoms were more frequent in patients with a posterior insular seizure onset. CONCLUSIONS: Seizure semiology is heterogeneous in pure insular-onset epilepsy. Differences between the anterior and posterior insular seizures reflect the functional organization of the insula. Particularly, the different types of motor symptoms may help to distinguish anterior from posterior insular seizure onset.

A Novel Digital Patient-Reported Outcome Platform for Head and Neck Oncology Patients-A Pilot Study.

INTRODUCTION: The patient's role in toxicity reporting is increasingly acknowledged. There is also a need for developing modern communication methods between the patient and the medical personnel. Furthermore, the increasing number of head and neck cancer (HNC) patients is reflected in the volume of treatment follow-up visits, which remains a challenge for the health care. Electronic patient-reported outcome (ePRO) measures may provide a cost-efficient way to organize follow-up for cancer patients. MATERIALS AND METHODS: We tested a novel ePRO application called Kaiku®, which enables real-time, online collection of patient-reported outcomes, such as side effects caused by treatment and quality of life. We conducted a pilot study to assess the suitability of Kaiku® for HNC patients at the Department of Oncology, Helsinki University Hospital, Helsinki, Finland. Patients used Kaiku® during and one month after radiotherapy to report treatment-related side effects and quality of life. Two physicians and a nurse performed the practical electronic communication part of the study. RESULTS: Five of the nine patients agreed to participate in the study: three of them had local early-stage larynx cancer (T2N0, T1aN0, and T2N0) and the remaining two patients had early-stage base of tongue cancer (T2N0 and T1N2b). The degree of side effects reported by the patients via Kaiku® ranged from mild to life threatening. The number of outcome data points on patients' progress was significantly increased, which resulted in a better follow-up and improved communication between the patient and the care team. CONCLUSIONS: Kaiku® seems to be a suitable tool to monitor side effects and quality of life during and after radiotherapy among HNC patients. Kaiku® and similar tools could be useful in organizing a cost-effective follow-up process for HNC patients. We recommend conducting a larger study to further assess the impact of an ePRO solution in routine clinical practice. ePRO solutions may aid in the follow-up for cancer patients.They seem suitable to monitor, for example, side effects and quality of life.These systems ensure fast patient-driven reporting.

[EEG under the surface]. / EEG pintaa syvemmältä.

Epilepsy work-up is based on history and scalp EEG. Drug resistant epilepsy should be evaluated in a dedicated epilepsy surgery unit. Sometimes non-invasive studies fail to localize the epileptogenic area in focal epilepsy and then the work up can be complemented with intracranial EEG. Intracranial electrodes are implanted either in the subdural space or intraparenchymally. This is followed by one to two weeks of EEG monitoring in a specialized videotelemetry unit. Intracranial EEG helps to define the borders of the epileptogenic area for resection. The ultimate objective is to render the patient seizure free. The outcome of resective epilepsy surgery depends on the etiology of epilepsy, localization of the epileptogenic area and MR image yield.

Increased indoleamine 2,3-dioxygenase (IDO) activity in idiopathic generalized epilepsy.

PURPOSE: Indoleamine 2,3-dioxygenase (IDO) is a cytokine-inducible enzyme that participates in tryptophan (trp) and serotonin metabolism with an ability to modulate neuroinflammation. Several recent studies have shown associations between cytokines and epilepsy. In this study we investigated whether activation of IDO is associated with epilepsy. METHODS: Kynurenine (kyn)/trp serum ratio, as an indicator of IDO activity was analyzed in 271 carefully classified epilepsy patients, and 309 healthy adults. RESULTS: IDO activity was increased in patients with unclassified idiopathic generalized epilepsy (IGE) (n=11; p=0.05), in juvenile myoclonic epilepsy (JME) (n=25; p=0.04) and in patients those with temporal lobe epilepsy but no hippocampal sclerosis (TLE-HS) (n=103; p=0.05) compared to the control subjects. In patients with idiopathic (but not cryptogenic or symptomatic) etiology of epilepsy, IDO activity was increased compared to the control subjects (p<0.05). Patients with extra-TLE or TLE+HS had IDO activity comparable to the control subjects. Patients who were one-month seizure-free prior to sampling had increased IDO activity compared to the control subjects (p=0.03). CONCLUSIONS: Increased IDO activity appeared to be associated with idiopathic generalized epilepsies such as unclassified IGE and JME, two of the most common types of primary generalized epilepsy. We also found a trend of increased IDO activity in patients with TLE-HS. Our results suggest that increased IDO activity may represent an adaptive metabolic phenomenon in epilepsy, which may also have a neuroprotective or anticonvulsive role by downregulating neuroinflammation in the brain.

The effect of surgery in encephalopathy with electrical status epilepticus during sleep.

PURPOSE: We analyzed clinical and electroencephalography (EEG) outcomes of 13 patients with pharmacoresistant encephalopathy with electrical status epilepticus during sleep (ESES) following epilepsy surgery. METHODS: All patients had symptomatic etiology of ESES and preoperative neuropsychological deterioration. Ten patients had daily atypical absences. Clinical outcome was assessed at 6 months and at 2 years after surgery. Clinical and EEG data were reviewed retrospectively. The spike propagation pattern and area and source strength in source montage were analyzed from preoperative and postoperative EEG studies. KEY FINDINGS: Preoperative sleep EEG showed electrical status epilepticus during sleep (SES) with one-way interhemispheric propagation in nine patients and with two-way interhemispheric propagation in four. The age of the patients at the time of surgery ranged from 3.6-9.9 years. Focal resection (two patients) or hemispherotomy (one patient with postoperative EEG) either terminated SES or restricted the discharge to one region. Either reduced SES propagation area or source strength was found in four of eight callosotomy patients with postoperative EEG. Of patients who had seizures preoperatively, Engel class I-II seizure outcome was observed in two of three children after focal resection or hemispherotomy and in two of eight children after callosotomy. None of these patients with Engel class I-II outcome had SES with two-way interhemispheric propagation on preoperative EEG. Cognitive deterioration was halted postoperatively in all except one patient. Cognitive catch-up of more than 10 IQ points was seen in three patients, all of whom had shown a first measured IQ of >75. SIGNIFICANCE: Patients with pharmacoresistant ESES based on symptomatic etiology may benefit from resective surgery or corpus callosotomy regarding both seizure outcome and cognitive prognosis.

Long-term outcome of 32 children with encephalopathy with status epilepticus during sleep, or ESES syndrome.

PURPOSE: To prospectively evaluate the efficacy of drug treatment and long-term cognitive outcome in children with encephalopathy with status epilepticus during sleep (ESESS). METHODS: Thirty-two children were diagnosed and prospectively followed up for at least 3 years at our unit between 1991 and 2007. Twenty-seven children were included in the prospective treatment study with valproate (VPA) and 17 with VPA combined with ethosuximide (ESM). Treatment response of disappearance of electrical status epilepticus during sleep (SES) was documented with overnight EEG recordings. Neuropsychological follow up for at least 5 years was available in 18 patients. RESULTS: Six children had atypical rolandic (AR) epilepsy, nine Landau-Kleffner syndrome (LKS), and 17 symptomatic epilepsy. Before ESESS, 20 children were cognitively normal. Prospective treatment with VPA and ESM was effective in 3 of the 17 children (18%) treated. Abolition of SES with drug treatment was observed in 16 patients. In all, 10 children (31%), 4 with AR (67%), 3 with LKS (33%), and 3 with symptomatic etiology (19%), including 9 with treatment response regained the pre-ESESS cognitive level. Unfavorable cognitive outcome was predicted by younger age at ESESS diagnosis, lower IQ at the time of the diagnosis, and no response to drug treatment when compared with those with favorable cognitive outcome. Eight of the 16 nonresponders underwent epilepsy surgery. DISCUSSION: Treatment response with VPA combined with ESM was observed more often than with other drug combinations. Most children with ESESS experienced permanent cognitive impairment. Cognitive outcome depends on treatment response on electroencephalography (EEG) and seizures, and on underlying etiology.

Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy.

PURPOSE: Glutamic acid decarboxylase antibodies (GADAs) have been detected in patients with epilepsy, but the clinical determinants of epilepsy associated with GADA have not been defined. METHODS: We analyzed GADA with a radioimmunoassay in sera of 253 well-characterized patients with epilepsy and 200 control subjects. The positive samples were confirmed by immunohistochemistry and western blotting (WB). Sera were screened for other autoantibodies. RESULTS: GADA were detected in 15 patients (5.9%) and in three control subjects (1.5%) (p = 0.026). Seven patients (2.8%) had high GADA titers [>or=1,000 relative units (RUs)/ml], six of whom had temporal lobe epilepsy (TLE). All three GADA-positive control subjects had low titers. Two of the five patients with high GADA titers and available cerebrospinal fluid (CSF) samples had intrathecal synthesis (IS) of GADA; one patient had CSF oligoclonal bands. The prevalence of increased levels of GADA tended to be higher in patients with TLE than in patients with extra-TLE [odds ratio (OR) 1.32, 95% confidence interval (CI) 0.39-4.42; p = 0.657]. The patients with high GADA titers had significantly higher number of other autoantibodies compared to the patients with low GADA titers (p = 0.001) and the patients with normal GADA (p < 0.001). DISCUSSION: High GADA titers were present in a subgroup of patients; close to 90% had TLE. The immunologic profile of these patients suggests that the most probable origin of their epilepsy is autoimmune. A positive IS of GADA may be a marker of an ongoing immune response that could identify those patients in whom a trial with immunosuppressive therapy might be warranted.

Interleukin-6 levels are increased in temporal lobe epilepsy but not in extra-temporal lobe epilepsy.

Previous studies have reported activation of inflammatory cytokines in seizures, but clinical characteristics of epilepsy associated with cytokine activation have not been well established. In this study, serum levels of interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA) were measured, and clinical characteristics of epilepsy were assessed in 86 well-evaluated patients with refractory focal epilepsy and in 5 patients with controlled focal epilepsy. Epilepsy was evaluated based on patient histories, electroclinical findings, and high-resolution brain MRI scans. Sixty-three healthy blood donors served as controls. IL-6 concentrations were chronically increased in epilepsy patients (11%) compared with healthy controls (0%) (P = 0.007). Increased levels of IL-6 were more prevalent in patients with temporal lobe epilepsy (TLE) compared to patients with extra-TLE (P = 0.028). Also the mean and the median serum levels of IL-6 were higher in patients with TLE than in patients with extra-TLE (P = 0.042). Concentrations of IL-1RA were not significantly different in patients compared with controls. Indicated by increased levels of IL-6 in TLE, epilepsy type is important in determining chronic overproduction of cytokines in refractory focal epilepsy. The results may reflect a chronic immunological process in the brain in patients with refractory epilepsy.

Seizure-freedom with combination therapy in localization-related epilepsy.

We analyzed the effect of combination therapy on seizure frequency in all adult patients (N=193) with focal epilepsy followed at a single institution in a cross-sectional study. One hundred and thirty-five patients were on two AEDs, of them, 37 (27%) were seizure-free, 50 patients were on three AEDs including 5 (10%) seizure-free patients (p<0.01 for seizure-freedom with two AEDs versus three AEDs). Thirty-five different combinations were used in patients on two AEDs and 40 combinations on patients on three drugs emphasizing the difficulties involved in evaluation of the efficacy and tolerability of specific combinations. The significant proportion of seizure-free cases (27%) on duotherapy is suggesting the usefulness of combination therapy in achieving seizure-freedom in epilepsies refractory to single drug treatment. The material in the study was not from a randomized trial and therefore the comparability of patients on different AEDs is uncertain, but on the other hand the clinical practice followed provides a natural experiment suitable for comparative, non-randomized assessment of treatment outcomes.