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.

Return to work following mild traumatic brain injury.

OBJECTIVE: To examine factors relating to return to work (RTW) following mild traumatic brain injury (mTBI). PARTICIPANTS: One hundred and nine patients (Age: M = 37.4 years, SD = 13.2; 52.3% women) who sustained an mTBI. DESIGN: Inception cohort design with questionnaires and neuropsychological testing completed approximately 3 to 4 weeks postinjury. SETTING: Emergency Department of Tampere University Hospital, Finland. MAIN OUTCOME MEASURES: Self-report (postconcussion symptoms, depression, fatigue, and general health) and neurocognitive measures (attention and memory). RESULTS: The cumulative RTW rates were as follows: 1 week = 46.8%, 2 weeks = 59.6%, 3 weeks = 67.0%, 4 weeks = 70.6%, 2 months = 91.7%, and 1 year = 97.2%. Four variables were significant predictors of the number of days to RTW: age, multiple bodily injuries, intracranial abnormality at the day of injury, and fatigue ratings (all P < .001). The largest amount of variance accounted for by these variables in the prediction of RTW was at 30 days following injury (P < .001, R = 0.504). Participants who returned to work fewer than 30 days after injury (n = 82, 75.2%) versus more than 30 days (n = 27, 24.8%) did not differ on demographic or neuropsychological variables. CONCLUSIONS: The vast majority of this cohort returned to work within 2 months. Predictors of slower RTW included age, multiple bodily injuries, intracranial abnormality at the day of injury, and fatigue.

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.

[Acute head injuries in primary health care--internet survey conducted with general practitioners]. / Pään vammat perusterveydenhuollossa--kyselytutkimus Pirkanmaan sairaanhoito- piirin terveyskeskuslääkäreille.

Patients with head injury constitute a large population treated in primary health care. It is essential to recognize patients with traumatic brain injury among this notable population to determine the need for more specific evaluation. General practitioners (n=331) in Pirkanmaa hospital district in Finland received an email link to answer the survey. The response rate was 54.1% (n=179). Mean survey score was 20.5 points (max. 25). Only acquaintance with the national traumatic brain injury practice guidelines was associated with greater survey scores. The general practitioners' level of knowledge in managing head injuries was good. Deficiencies were found in the questions dealt with post-traumatic amnesia and the definition of traumatic brain injury.

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.

Reliability, validity and clinical usefulness of the BNI fatigue scale in mild traumatic brain injury.

OBJECTIVES: The purpose of this study was to examine the reliability, validity and clinical usefulness of the Barrow Neurological Institute Fatigue Scale (BNI-FS) in patients with mild traumatic brain injuries (MTBI). METHODS AND PROCEDURE: Participants were 125 patients enrolled from the Emergency Department (ED) of Tampere University Hospital, Finland who had sustained an MTBI. The average number of days from injury to the interview and questionnaires was 24.1 (SD = 5.4, Range = 8-38). The patients were compared to a healthy control sample. Patients completed the Barrow Neurological Institute Fatigue Scale, Fatigue Impact Scale (FIS), Beck Depression Inventory-Second Edition (BDI-II), Rivermead Post-concussion Symptom Questionnaire (RPSQ) and the health assessment measure EuroQol five Dimension (EQ-5D) Visual Analogue Scale (VAS). RESULTS: The MTBI group had significantly greater total scores on the BNI-FS than the control group (p < 0.005, Cohen's d = 0.40). The internal consistency reliability for the BNI-FS, as measured by Cronbach's alpha, was 0.96 for the MTBI group and 0.87 for the control group. The 10 items were submitted to an exploratory principal components factor analysis with varimax rotation in the MTBI group. A one-factor solution, accounting for 73.3% of the total variance, appropriately summarized the data. The correlation between the BNI-FS and other measures was rs = 0.68 (p < 0.001) for the BDI-II, rs = 0.68 (p < 0.001) for the RPSQ, rs = -0.39 (p < 0.001) for the EQ-5D VAS and rs = 0.84 (p < 0.001) for the FIS. Fatigue ratings correlated positively with number of days post-injury before returning to work (rs = 0.27, p < 0.006). CONCLUSION: The BNI-FS is a relatively new, brief and highly reliable measure of fatigue.

[Treatment of non-convulsive status epilepticus]. / Nonkonvulsiivisen status epilepticuksen hoito.

Non-convulsive status epilepticus is an insidious condition and a challenging diagnosis for neurologists on call. The condition must, however, be recognized, since it constitutes a neurological emergency. Non-convulsive status epilepticus may also be associated as an additional complication with an acute neurologic disease, in which case an EEG recording is usually required. In addition, non-convulsive status epilepticus can be found in a significant proportion of patients with unconsciousness of unknown origin.

[Mild brain injuries in emergency medicine]. / Lievät aivovammat päivystyslääketieteessä.

Diagnostics and correct classification of mild brain injuries is challenging. Problems caused by insufficient documentation at the acute phase become more obvious in situations in which legal insurance issues are to be considered. A small proportion of patients with mild brain injury suffer from prolonged symptoms. Medical recording and classification of the brain injury at the initial phase should therefore be carried out in a structured manner. The review deals with the diagnostic problems of mild brain injuries and presents a treatment protocol for adult patients at the acute phase, aiming at avoiding prolonged problems.

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.

Texture analysis of MR images of patients with mild traumatic brain injury.

BACKGROUND: Our objective was to study the effect of trauma on texture features in cerebral tissue in mild traumatic brain injury (MTBI). Our hypothesis was that a mild trauma may cause microstructural changes, which are not necessarily perceptible by visual inspection but could be detected with texture analysis (TA). METHODS: We imaged 42 MTBI patients by using 1.5 T MRI within three weeks of onset of trauma. TA was performed on the area of mesencephalon, cerebral white matter at the levels of mesencephalon, corona radiata and centrum semiovale and in different segments of corpus callosum (CC) which have been found to be sensitive to damage. The same procedure was carried out on a control group of ten healthy volunteers. Patients' TA data was compared with the TA results of the control group comparing the amount of statistically significantly differing TA parameters between the left and right sides of the cerebral tissue and comparing the most discriminative parameters. RESULTS: There were statistically significant differences especially in several co-occurrence and run-length matrix based parameters between left and right side in the area of mesencephalon, in cerebral white matter at the level of corona radiata and in the segments of CC in patients. Considerably less difference was observed in the healthy controls. CONCLUSIONS: TA revealed significant changes in texture parameters of cerebral tissue between hemispheres and CC segments in TBI patients. TA may serve as a novel additional tool for detecting the conventionally invisible changes in cerebral tissue in MTBI and help the clinicians to make an early diagnosis.

GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies.

BACKGROUND: Autoantibodies against the smaller isoform of glutamate decarboxylase (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several neurological disorders, including Stiff Person Syndrome (SPS). GAD65Ab are also reported in cases of epilepsy, indicating an autoimmune component. GAD65Ab in patients with co-occurring T1D, epilepsy or SPS may be part of either autoimmune pathogenesis. To dissect the etiologies associated with GAD65Ab, we analyzed GAD65Ab titer, epitope specificity and enzyme inhibition in GAD65Ab-positive patients diagnosed with epilepsy (n = 28), patients with epilepsy and T1D (n = 10), patients with SPS (n = 20), and patients with T1D (n = 42). RESULTS: GAD65Ab epitope pattern in epilepsy differed from T1D and SPS patients. Four of 10 patients with co-occurring T1D and epilepsy showed GAD65Ab profiles similar to T1D patients, while lacking GAD65Ab characteristics found in GAD65Ab-positive epilepsy patients. One of these patients responded well to anti-epileptic drugs (AEDs), while another patient did not require medication for seizure control. The third patient was refractory due to a diagnosis of meningioma. The response of the remaining patient to AEDs was unknown. GAD65Ab in the remaining six patients with T1D and epilepsy showed profiles similar to those in epilepsy patients. CONCLUSIONS: Different autoimmune responses associated with T1D, epilepsy and SPS are reflected by disease-specific GAD65Ab patterns. Moreover, the epileptic etiology in patients diagnosed with both T1D and epilepsy may present two different etiologies regarding their epileptic condition. In one group T1D co-occurs with non-autoimmune epilepsy. In the other group GAD65Ab are part of an autoimmune epileptic condition.

The concentration of cell-free DNA in video-EEG patients is dependent on the epilepsy syndrome and duration of epilepsy.

OBJECTIVE: Cell-free DNA (cf-DNA) is a marker of inflammation and cell death. The purpose of the present study was to analyze the role of cf-DNA as a putative biomarker in refractory epilepsy. METHODS: Baseline concentration of cf-DNA was measured in the serum of 51 carefully evaluated refractory epilepsy patients undergoing video-EEG monitoring. Epilepsy was classified based on seizure semiology, patient history, and imaging findings. Majority of the patients (47) had focal epilepsy. The association of the concentration cf-DNA with different clinical determinants was analyzed. 250 healthy individuals served as control subjects. RESULTS: The mean baseline concentration of cf-DNA was lower in patients with extra temporal lobe epilepsy (XTLE) compared to control subjects (0.72 µg/ml vs. 0.80 µg/ml; p = 0.001). The difference in concentration of cf-DNA between patients with temporal lobe epilepsy (TLE) and control subjects was not significant. The maximum concentration of cf-DNA after baseline measurement was significantly lower in patients with duration of epilepsy ≥ 18 years compared to those with duration of epilepsy < 18 years (0.022 µg/ml vs. 0.031 µg/ml; p = 0.044). The maximum concentration of cf-DNA was higher in patients with body mass index (BMI) ≥ 25 compared to those with BMI < 25 (0.004 µg/ml vs. 0.041 µg/ml; p = 0.006). DISCUSSION: The difference in cf-DNA concentration between patients with XTLE and control subjects strengthens the previous observations of the importance of epilepsy type with regard of different biomarkers.

A prospective biopsychosocial study of the persistent post-concussion symptoms following mild traumatic brain injury.

This study examined multiple biopsychosocial factors relating to post-concussion symptom (PCS) reporting in patients with mild traumatic brain injuries (mTBI), including structural (computed tomography and magnetic resonance imaging [MRI]) and microstructural neuroimaging (diffusion tensor imaging [DTI]). Patients with mTBIs completed several questionnaires and cognitive testing at approximately one month (n=126) and one year (n=103) post-injury. At approximately three weeks post-injury, DTI was undertaken using a Siemens 3T scanner in a subgroup (n=71). Measures of fractional anisotropy were calculated for 16 regions of interest (ROIs) and measures of apparent diffusion coefficient were calculated for 10 ROIs. Patients were compared with healthy control subjects. Using International Classification of Diseases, Tenth Revision (ICD-10) PCS criteria and mild or greater symptom reporting, 59% of the mTBI sample met criteria at one month and 38% met criteria at one year. However, 31% of the healthy control sample also met criteria for the syndrome-illustrating a high false-positive rate. Significant predictors of ICD-10 PCS at one month were pre-injury mental health problems and the presence of extra-cranial bodily injuries. Being symptomatic at one month was a significant predictor of being symptomatic at one year, and depression was significantly related to PCS at both one month and one year. Intracranial abnormalities visible on MRI were present in 12.1% of this sample, and multifocal areas of unusual white matter as measured by DTI were present in 50.7% (compared with 12.4% of controls). Structural MRI abnormalities and microstructural white matter findings were not significantly associated with greater post-concussion symptom reporting. The personal experience and reporting of post-concussion symptoms is likely individualized, representing the cumulative effect of multiple variables, such as genetics, mental health history, current life stress, medical problems, chronic pain, depression, personality factors, and other psychosocial and environmental factors. The extent to which damage to the structure of the brain contributes to the persistence of post-concussion symptoms remains unclear.

Lack of antibodies to NMDAR or VGKC-complex in GAD and cardiolipin antibody-positive refractory epilepsy.

BACKGROUND: Over the last few years autoantibodies against neuronal proteins have been identified in several forms of autoimmune encephalitis and epilepsy. NMDA receptor (NMDAR) and voltage gated potassium channel (VGKC) complex antibodies are mainly associated with limbic encephalitis (LE) whereas glutamic acid decarboxylase antibodies (GADA) and anticardiolipin (ACL) antibodies are more commonly detected in patients with chronic epilepsy. Clinical features vary between these antibodies suggesting the specificity of different neuronal antibodies in seizures. METHODS: Serum samples of 14 GADA positive and 24 ACL positive patients with refractory epilepsy were analyzed for the presence of VGKC or NMDAR antibodies. RESULTS: No positive VGKC or NMDAR antibodies were found in these patients. CONCLUSIONS: The results confirm the different significance of these neuronal antibodies in seizure disorders. Different autoantibodies have different significance in seizures and probably have different pathophysiological mechanisms of actions.

Necessity of monitoring after negative head CT in acute head injury.

OBJECTIVE: The main objective of this study was to evaluate the incidence of delayed complications in acute head injury (HI) patients with an initial normal head computed tomography (CT). MATERIALS AND METHODS: This retrospective study included 3023 consecutive patients who underwent head CT due to an acute HI at the Emergency Department (ED) of Tampere University Hospital (August 2010-July 2012). Regardless of clinical injury severity, the patients with a normal head CT were selected (n=2444, 80.9%). The medical records of these patients were reviewed to identify the individuals with a serious clinically significant complication related to the primary HI. The time window considered was the following 72h after the primary head CT. A repeated head CT in the hospital ward, death, or return to the ED were indicative of a possible complication. RESULTS: The majority (n=1811, 74.1%) of the patients with a negative head CT were discharged home and 1.1% (n=27) of these patients returned to ED within 72h post-CT. A repeated head CT was performed on 12 (44.4%) of the returned patients and none of the scans revealed an acute lesion. Of the 632 (25.9%) CT-negative patients admitted to the hospital ward from the ED, a head CT was repeated in 46 (7.3%) patients within 72h as part of routine practice. In the repeated CT sample, only one (0.2%) patient had a traumatic intracranial lesion. This lesion did not need neurosurgical intervention. The overall complication rate was 0.04%. CONCLUSION: In the present study, which includes head injuries of all severity, the probability of delayed life-threatening complications was negligible when the primary CT scan revealed no acute traumatic lesions.

Clinical significance of treatment delay in status epilepticus.

BACKGROUND: Status epilepticus (SE) is a medical emergency that requires immediate action. The clinical and demographic features of SE are known to be highly variable. The objective of this study was to analyze the effect of treatment delays on patient recovery and different clinical factors that are important in the determination of the acute prognosis in SE. METHODS: This population-based study included 109 consecutive visits of patients with the diagnosis of SE in the emergency department (ED) of Tampere University Hospital. The clinical features of SE were compared with the discharge condition. RESULTS: The treatment delays were long; in half of the patients, the delay for paramedic arrival was over 30 min, and in one-third of the cases, the delay was over 24 h. ED patients who had less than 1 h of delay before the administration of an antiepileptic drug (AED) had better outcomes compared to patients with a greater than 1 h delay (p < 0.05). The two major etiologies for the SE were cerebrovascular disease and alcohol misuse. A good immediate outcome was found in 46% of the patients. Epileptiform activity on the EEG, a history of epilepsy or SE, presence of cardiovascular disease, and alcohol misuse were associated with a poor outcome. CONCLUSIONS: The results of this study emphasize the importance of an urgent response by emergency services and proper recognition of atypical phenotypes of SE.

High concentration of immunoglobulin A is associated with temporal lobe epilepsy.

INTRODUCTION: Dysfunction of immunoglobulins (Igs) has been detected in association with antiepileptic drugs (AEDs) and in newly diagnosed epilepsy patients. The aim of this study was to evaluate the effect of clinical features and the current or past use of AEDs on serum Ig concentrations in a well-examined group of patients with refractory epilepsy. PATIENTS AND METHODS: Using a nephelometric method, concentrations of IgA, IgG and IgM were analyzed in the sera of 257 patients with refractory epilepsy, 15 patients with controlled epilepsy and 584 healthy control subjects. RESULTS: A low IgA concentration was found in 8.8% of the patients with epilepsy compared with 1.9% of the control subjects. High concentrations of IgA were associated with temporal lobe epilepsy (TLE) compared with other epilepsy types (p=0.042). The high concentrations of IgA (p=0.042), low concentrations of IgG (p=0.002), and high concentrations of IgG (p=0.008) were also associated with autoimmune diseases. The use of lamotrigine, nitrazepam, oxcarbazepine, topiramate and valproic acid was associated with alterations in Ig concentrations. Current use of topiramate was associated with high serum IgG and IgM concentrations (OR 10.39; 95% CI: 3.08-35.04 and OR 7.02; 95% CI: 1.25-39.55, respectively). DISCUSSION: The finding of high serum IgA concentration in patients with TLE strengthens the previously found association of immunological activity in the epileptic temporal lobe rather than other brain regions. The newly observed immunological effects of topiramate are important to proper AED choice in patients with refractory epilepsy.

The concentration of cell-free DNA in focal epilepsy.

BACKGROUND: Increased production of cell-free DNA (cf-DNA), a marker of inflammation, cell death and degeneration, has been observed in stroke and severe traumatic brain injury among other medical conditions. The purpose of the present study was to evaluate the significance of cf-DNA in patients with focal epilepsy. METHODS: cf-DNA was measured in 167 consecutive well-evaluated patients with focal epilepsy (147 with refractory epilepsy). Epilepsy was characterized based on the patient history, electroclinical findings, neuroimaging results and etiology. 250 healthy individuals served as control subjects. RESULTS: The majority of the patients (125/167; 74.8%) had increased concentrations of cf-DNA. The median concentration of cf-DNA was significantly higher in the patients (0.867 µg/ml) compared to the control group (0.759 µg/ml) (p<0.001). Symptomatic etiology was associated with increased concentrations of cf-DNA compared to probably symptomatic etiology (p=0.036). CONCLUSIONS: The study confirms that the release of cf-DNA is more active in symptomatic refractory focal epilepsy, whereas this process is less pronounced in patients with unknown cause of epilepsy.

Immunological perspectives of temporal lobe seizures.

The temporal lobes are affected in many different neurological disorders, such as neurodegenerative diseases, viral and immunological encephalitides, and epilepsy. Both experimental and clinical evidence suggests a different inflammatory response to seizures in patients with temporal lobe epilepsy (TLE) in comparison to those with extra-TLE (XTLE). Proinflammatory cytokines and several autoantibodies have been shown to be associated with TLE compared to other epilepsy types suggesting the specific role and structure of the temporal lobe. Abundant experience suggests that activation of both innate and adaptive immunity is associated with epilepsy, particularly refractory focal epilepsy. Limbic encephalitis often triggers temporal lobe seizures, and a proportion of these disorders are immune-mediated. Histological evidence shows activation of specific inflammatory pathways in resected temporal lobes of epileptic patients, and certain epileptic disorders have shown increased incidence in patients with autoimmune diseases. Rapid activation of proinflammatory cytokines is observed after single seizures, but there is also evidence of chronic overproduction of cytokines and other inflammatory mediators in patients with TLE, suggesting a neuromodulatory role of inflammation in epilepsy. In this review we summarize current data on the presence and the role of immunological factors in temporal lobe seizures, and their possible involvement in epileptogenesis.

Outcome from Complicated versus Uncomplicated Mild Traumatic Brain Injury.

Objective. To compare acute outcome following complicated versus uncomplicated mild traumatic brain injury (MTBI) using neurocognitive and self-report measures. Method. Participants were 47 patients who presented to the emergency department of Tampere University Hospital, Finland. All completed MRI scanning, self-report measures, and neurocognitive testing at 3-4 weeks after injury. Participants were classified into the complicated MTBI or uncomplicated MTBI group based on the presence/absence of intracranial abnormality on day-of-injury CT scan or 3-4 week MRI scan. Results. There was a large statistically significant difference in time to return to work between groups. The patients with uncomplicated MTBIs had a median of 6.0 days (IQR = 0.75-14.75, range = 0-77) off work compared to a median of 36 days (IQR = 13.5-53, range = 3-315) for the complicated group. There were no significant differences between groups for any of the neurocognitive or self-report measures. There were no differences in the proportion of patients who (a) met criteria for ICD-10 postconcussional disorder or (b) had multiple low scores on the neurocognitive measures. Conclusion. Patients with complicated MTBIs took considerably longer to return to work. They did not perform more poorly on neurocognitive measures or report more symptoms, at 3-4 weeks after injury compared to patients with uncomplicated MTBIs.