Blood sampling via a peripheral artery catheter decreases cerebral oxygenation index in very low-birthweight infants.

AIM: This study evaluated the impact of blood sampling via peripheral arterial catheters on cerebral oxygenation and blood volume as a function of blood sampling velocity. METHODS: Near-infrared spectroscopy was applied to 20 very low-birthweight infants during peripheral arterial blood sampling. Changes in cerebral oxygenated, deoxygenated and total haemoglobin, cerebral blood volume and cerebral oxygenation index were recorded. Heart rate and oxygen saturation were measured continuously. To assess the impact of blood sampling velocity, both fast 40-sec and slow 70-sec sampling procedures were performed in a crossover study design, in which the order of sampling velocities was randomised for each patient. RESULTS: Both fast and slow blood sampling procedures resulted in a significant decrease in cerebral oxygenation index (fast, p = 0.002, slow, p = 0.008), and an increase in mean heart rate (both p = 0.02) and mean blood pressure (p = 0.02 and 0.04). Oxygenated and total haemoglobin and cerebral blood volume only decreased significantly after slow blood sampling (p < 0.001). CONCLUSION: Blood sampling from peripheral arterial catheters leads to significant fluctuations in cerebral oxygenation independent of the sampling velocity. Changes are comparable to those reported from umbilical blood sampling. We advise that blood sampling should be restricted as much as possible.

Levetiracetam but not valproate inhibits function of CD8+ T lymphocytes.

PURPOSE: To further elucidate possible immune-modulatory effects of valproate (VPA) or levetiracetam (LEV), we investigated their influence on apoptosis and cytotoxic function of CD8+ T lymphocytes in humans. METHODS: In 15 healthy subjects (9 female (60%), 35.7±12.1 years), apoptosis and cytotoxic function of CD8+ T lymphocytes were measured using flow cytometry following in vitro exposure to LEV (5 mg/L and 50 mg/L) and VPA (10mg/L and 100 mg/L). Apoptosis rates were determined after incubation with LEV or VPA for 1 h or 24 h. Cytotoxic function was assessed following 2h stimulation with mixed virus peptides, using perforin release, CD107a/b expression and proliferation. The presence of synaptic vesicle protein 2A (SV2A) was investigated in human CD8+ T lymphocytes by flow cytometry analysis, Western blot and real time polymerase chain reaction (rtPCR). RESULTS: High concentration of LEV decreased perforin release of CD8+ T lymphocytes (LEV 50 mg/L vs. CEF only: 21.4% (interquartile range (IQR) 16.5-35.9%) vs. 16.6% (IQR 12-24.9%), p=0.002). LEV had no influence on apoptosis and proliferation (p>0.05). VPA (100 mg/L) slowed apoptosis of CD8() T lymphocytes after 24h (VPA 100mg/L vs. control: 7.3% (IQR 5.4-9.5%) vs. 11.3% (IQR 8.2-15.1%), p<0.001), but had no effects on perforin release (p>0.05). SV2A protein was detected in CD8+ T lymphocytes. CONCLUSION: LEV decreased degranulation of CD8+ T lymphocytes which may contribute to the increased incidence of upper respiratory tract infections in LEV treated patients. Inhibition of SV2A may be responsible for this effect.

A female adult with Sandifer's syndrome and hiatal hernia misdiagnosed as epilepsy with focal seizures.

Sandifer's syndrome is a rare, probably underdiagnosed, and usually pediatric movement disorder associated with gastroesophageal reflux disease. Often, it is misdiagnosed as epilepsy or paroxysmal dyskinesia. We report the case of an adult female with Sandifer's syndrome initially diagnosed as focal epilepsy and treated inefficiently with anticonvulsants for two years.

Cytokines and epilepsy.

Epilepsy is a common chronic neurological disorder affecting approximately 8 out of 1000 people. Its pathophysiology, however, has remained elusive in many regards. Consequently, adequate seizure control is still lacking in about one third of patients. Cytokines are soluble mediators of cell communication that are critical in immune regulation. In recent years, studies have shown that epileptic seizures can induce the production of cytokines, which in turn influence the pathogenesis and course of epilepsies. At the time of this review, the focus is mostly on interleukin-1beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα). In this review, we summarize the current knowledge regarding these cytokines and their potential roles in epilepsy. The focus concentrates on their expression and influence on induced seizures in animal models of epilepsy, as well as findings in human studies. Both proconvulsive and anticonvulsive effects have been reported for each of these molecules. One possible explanation for this phenomenon is that cytokines play dichotomous roles through multiple pathways, each of which is dependent on free concentration and available receptors. Furthermore, the immune-mediated leakage in the blood-brain-barrier also plays an important role in epileptogenesis. Nonetheless, these observations demonstrate the multifarious nature of cytokine networks and the complex relationship between the immune system and epilepsy. Future studies are warranted to further clarify the influence of the immune system on epilepsy and vice versa.

Interictal alterations of cytokines and leukocytes in patients with active epilepsy.

BACKGROUND: Involvement of the innate immune system in the pathogenesis of epilepsies has been suggested but possible interactions between the immune system and human epilepsy remain unclear. We analyzed the interictal immuno-phenotype of leukocyte subsets and proinflammatory cytokine profiles in epileptic patients and correlated them with the epilepsy syndrome. METHODS: 101 patients with active focal or generalized epilepsy were prospectively included and compared to 36 healthy controls. Immuno-phenotype of leukocyte subsets and cytokines IL-1ß, IL-6 and tnfα were measured in peripheral blood. Multivariate analyses were performed to test group differences. RESULTS: As compared to controls, the patients showed an elevated percentage of monocytes (18.06±7.08% vs. 12.68±4.55%, p<0.001), NK cells (14.88±7.08% vs. 11.43±5.41%, p=0.019) and IL-6 concentration (3.33±3.11 pg/ml vs. 1.5±1.36 pg/ml, p=0.002). This remained true when focal epilepsies or generalized epilepsies were compared separately to controls but only focal epilepsies showed additionally a decrease in B lymphocyts (8.16±3.76% vs. 11.54±4.2%, p<0.001). Treatment with lamotrigine was associated with a higher percentage of B lymphocytes and valproate with an increased percentage of CD4(+) T lymphocytes. Therapy with levetiracetam showed a trend towards decreased CD8(+) T cell counts. No significant differences were seen between focal and generalized epilepsies and between temporal and extratemporal lobe epilepsies. CONCLUSION: Patients with active epilepsy revealed interictal alterations of the immune system which varied among specific syndromes and were influenced by antiepileptic drug treatment.

Localizing and lateralizing value of ictal flatulence.

OBJECTIVE: Autonomic seizures have been associated with seizure onset in the temporal or insular lobe and consist of variations in blood pressure and heart rate, sweating, flushing, piloerection, hypersalivation, vomiting, spitting, and alterations in bladder and bowel functions. The aim of this study was to evaluate the localizing and lateralizing value of ictal flatulence. METHODS: Medical records of patients with focal epilepsies who were monitored at the Interdisciplinary Epilepsy Center Marburg between 2006 and 2009 were reviewed for the occurrence of ictal flatulence. Clinical, electrophysiological, and imaging data were reviewed and compared with data for previously reported cases of ictal flatulence. RESULTS: Two patients with ictal flatulence were identified (0.6%). In both patients, ictal flatulence was associated with a seizure pattern in the temporal lobe of the dominant hemisphere. Our cases and previously reported cases point toward activation of insular cortex because of such additional autonomic symptoms as unilateral piloerection, tachycardia, profound sweating, and flushing of the face. CONCLUSIONS: Ictal flatulence is a rare manifestation of autonomic seizures and a localizing sign for temporal or/and insular lobe epilepsies. In general, ictal flatulence seems to have no lateralizing value.

Six months of postmarketing experience with adjunctive lacosamide in patients with pharmacoresistant focal epilepsy at a tertiary epilepsy center in Germany.

We report our 6 months of experience with adjunctive lacosamide in 25 patients with pharmacoresistant focal epilepsy. Baseline characteristics of our patients were similar to those of the populations in the three clinical trials that evaluated lacosamide for refractory focal epilepsy. One patient experienced sustained seizure freedom for 5 months; two more patients had nonsustained periods of seizure freedom of 1 and 4 months. A total of eight patients (32%) reported a greater than 50% reduction in seizure frequency. Thirteen patients (52%) reported side effects during the titration, mostly dizziness, fatigue, nausea, and gait instability. In five patients (20%), these disappeared during the maintenance phase and/or with dose reduction. Two patients lost more than 10% of their body weight. Otherwise, in terms of efficacy and adverse effects, our data mirror the profile of lacosamide described in the three clinical trials. Substantial weight loss may occur in individual patients.

Etiology and site of temporal lobe epilepsy influence postictal cytokine release.

Inflammatory mechanisms are involved in the pathogenesis of epilepsy. Vice versa, immune functions are regulated by the brain. We measured postictal changes in serum levels of the immuno-modulating cytokines IL-1beta, IL-6 and TNFalpha in patients with well-defined temporal lobe epilepsy (TLE) and determined modifying factors. Serum levels of IL-1beta, IL-6 and TNFalpha were quantified by ELISA at baseline as well as immediately, 1h and 24h after a complex partial (CPS) or secondary generalized tonic-clonic seizure (GTCS) during video-EEG monitoring in 25 patients suffering from temporal epilepsy. IL-6 increased by 51% immediately after the seizure (p<0.01) and remained elevated for 24h. This increase lacked in patients with hippocampal sclerosis (HS; n=16, mean increase 28%, p>0.5, vs. 112%, p<0.01 in patients without HS). IL-6 levels were higher after right-sided seizures as compared to left-sided seizures 24h after the seizure (8.7pg/mL vs. 3.4pg/mL, p<0.05). In patients taking valproate (VPA, n=9), the levels of IL-1beta were higher as compared to patients not treated with VPA. The results suggest a relationship between the cytokine system and characteristics of TLE such as side and pathology.

NK and CD4+ T cell changes in blood after seizures in temporal lobe epilepsy.

UNLABELLED: Immunological phenomena may affect the course of focal epilepsy. We analyzed prospectively the pre- and postictal distribution of leukocyte subsets in epileptic patients. METHODS: Twenty-two patients (age 36.6+/-10.8 years, 50% men) with temporal lobe epilepsy were included. Distribution of leukocyte subsets and serum levels of epinephrine were measured in peripheral blood immediately and 24 h after seizures and compared to baseline values. RESULTS: In the immediate postictal state (10+/-6 min), we observed a significant relative increase of total leukocytes (42%, p=0.0004), neutrophil leukocytes (55%, p=0.0007), total lymphocytes (45%, p=0.0019), natural killer (NK) cells (104%, p=0.0017), and epinephrine (454%, p=0.0014). CD4(+) T cells decreased by 13% (p=0.0113). These postictal changes remained significant considering only complex partial seizures (n=17). The alterations were more pronounced in patients with hippocampal sclerosis. Treatment with valproic acid (VPA) was accompanied by a greater postictal decrease of CD4(+) T cells (25% compared to 5% in patients without VPA, p=0.041) while treatment with levetiracetam (LEV) correlated with a low postictal increase of NK-like T cells (4% versus 41%, p=0.016). Twenty-four hours after the seizures the alterations had resolved. CONCLUSION: Profound postictal changes in the immune cell composition of the peripheral blood may have been mediated by epinephrine release. The greater immune response in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis may reflect a close relationship between mesial temporal structures and the sympathetic nerve system. VPA and LEV may have an impact on seizure induced immunological changes.