Reply to comments on "Performance of a seizure warning algorithm based on the dynamics of intracranial EEG" by Mormann, F., Elger, C.E., and Lehnertz, K.
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Algorithms↗
Biomedical subjects
J Chris Sackellares
Publications and source records attributed to J Chris Sackellares.
Affect in patients with epilepsy undergoing video/EEG monitoring: retrospective versus momentary assessment and temporal relationship to seizures.
This study was designed to (1) compare retrospective and momentary assessments of mood/affect, and (2) examine the temporal relationship between affect and seizure occurrence. Patients with epilepsy undergoing long-term video/EEG monitoring (LTM) completed an affect rating of how they felt "at that moment" each time a programmed watch beeped (momentary assessment); these ratings were averaged across each patient's hospital stay. Prior to discharge, patients were asked to think back and rate how they felt "during their hospital stay" using the same rating scale (retrospective assessment). Results indicated that patients retrospectively recalled feeling significantly more positive during their LTM than they reported feeling when they were actually undergoing LTM. Among patients who had EEG-verified seizures, momentary assessments were used to compare affect during the interictal periods with affect during the prodromal and postictal periods. The latter two periods were characterized by significantly less activated positive affect than were the interictal periods.
Adult↗
Predictability analysis for an automated seizure prediction algorithm.
Epileptic seizures of mesial temporal origin are preceded by changes in signal properties detectable in the intracranial EEG. A series of computer algorithms designed to detect the changes in spatiotemporal dynamics of the EEG signals and to warn of impending seizures have been developed. In this study, we evaluated the performance of a novel adaptive threshold seizure warning algorithm (ATSWA), which detects the convergence in Short-Term Maximum Lyapunov Exponent (STLmax) values among critical intracranial EEG electrode sites, as a function of different seizure warning horizons (SWHs). The ATSWA algorithm was compared to two statistical based naïve prediction algorithms (periodic and random) that do not employ EEG information. For comparison purposes, three performance indices "area above ROC curve" (AAC), "predictability power" (PP) and "fraction of time under false warnings" (FTF) were defined and the effect of SWHs on these indices was evaluated. The results demonstrate that this EEG based seizure warning method performed significantly better (P < 0.05) than both naïve prediction schemes. Our results also show that the performance indexes are dependent on the length of the SWH. These results suggest that the EEG based analysis has the potential to be a useful tool for seizure warning.
Adult↗
Comment on "Inability of Lyapunov exponents to predict epileptic seizures".
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Dynamical resetting of the human brain at epileptic seizures: application of nonlinear dynamics and global optimization techniques.
Epileptic seizures occur intermittently as a result of complex dynamical interactions among many regions of the brain. By applying signal processing techniques from the theory of nonlinear dynamics and global optimization to the analysis of long-term (3.6 to 12 days) continuous multichannel electroencephalographic recordings from four epileptic patients, we present evidence that epileptic seizures appear to serve as dynamical resetting mechanisms of the brain, that is the dynamically entrained brain areas before seizures disentrain faster and more frequently (p < 0.05) at epileptic seizures than any other periods. We expect these results to shed light into the mechanisms of epileptogenesis, seizure intervention and control, as well as into investigations of intermittent spatiotemporal state transitions in other complex biological and physical systems.
Adaptation, Physiological↗
Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures.
PURPOSE: This study was designed to evaluate efficacy and safety of zonisamide (ZNS) as adjunctive treatment for patients with refractory partial seizures. METHODS: This randomized, double-blind, placebo-controlled study was conducted at four epilepsy treatment centers. It included a baseline phase (8 to 12 weeks) and a double-blind treatment phase (12 weeks). Initially, patients randomized to ZNS treatment were given a 7-mg/kg/d dosage. When investigators found that adverse effects could be reduced by gradually introducing ZNS, patients were allowed to begin treatment at lower doses (100 mg or approximately 1.5 mg/kg/d) titrated over several weeks to a maximum of 400 to 600 mg/d. Primary and secondary efficacy measures were the median percentage reduction from baseline in seizure frequency and the proportion of patients achieving a > or =50% reduction from baseline (responder rate). Patient and physician global assessments also served as indicators of efficacy. Safety was assessed primarily by treatment-emergent adverse events. RESULTS: ZNS-treated patients had a 28.9% reduction in seizure frequency, which differed significantly from the 4.7% increase in placebo-treated patients. The responder rate for ZNS-treated patients was 26.9%, compared with 16.2% for placebo-treated patients. At study's end, 66.2% of ZNS-treated patients and 12.3% of placebo-treated patients considered their condition improved; similarly, physicians assessed 63.6% of ZNS-treated patients and 10.8% of placebo-treated patients as improved. The most frequently reported adverse events with ZNS treatment included somnolence, irritability, dizziness, nausea, and fatigue. CONCLUSIONS: As adjunctive treatment, ZNS was generally well tolerated and significantly improved seizure control among patients with refractory partial seizures.
Adolescent↗
Adaptive epileptic seizure prediction system.
Current epileptic seizure "prediction" algorithms are generally based on the knowledge of seizure occurring time and analyze the electroencephalogram (EEG) recordings retrospectively. It is then obvious that, although these analyses provide evidence of brain activity changes prior to epileptic seizures, they cannot be applied to develop implantable devices for diagnostic and therapeutic purposes. In this paper, we describe an adaptive procedure to prospectively analyze continuous, long-term EEG recordings when only the occurring time of the first seizure is known. The algorithm is based on the convergence and divergence of short-term maximum Lyapunov exponents (STLmax) among critical electrode sites selected adaptively. A warning of an impending seizure is then issued. Global optimization techniques are applied for selecting the critical groups of electrode sites. The adaptive seizure prediction algorithm (ASPA) was tested in continuous 0.76 to 5.84 days intracranial EEG recordings from a group of five patients with refractory temporal lobe epilepsy. A fixed parameter setting applied to all cases predicted 82% of seizures with a false prediction rate of 0.16/h. Seizure warnings occurred an average of 71.7 min before ictal onset. Similar results were produced by dividing the available EEG recordings into half training and testing portions. Optimizing the parameters for individual patients improved sensitivity (84% overall) and reduced false prediction rate (0.12/h overall). These results indicate that ASPA can be applied to implantable devices for diagnostic and therapeutic purposes.
Algorithms↗
Lamotrigine monotherapy improves health-related quality of life in epilepsy: a double-blind comparison with valproate.
The effects of monotherapy with lamotrigine on health-related quality of life were compared with those of valproate monotherapy in a randomized, double-blind trial designed to evaluate treatment-emergent weight changes in patients with epilepsy. At the end of 8 months of treatment, significantly more patients using lamotrigine compared with valproate experienced quality-of-life improvements on the Health Perceptions (42% vs 15%), Energy/Fatigue (47% vs 28%), and Social Isolation (35% vs 16%) subscales of the Quality of Life in Epilepsy-89 (QOLIE-89) questionnaire (P<0.05). Compared with valproate-treated patients, lamotrigine-treated patients were four times more likely to experience improvement in Health Perceptions, 2.3 times more likely to experience improvement in Energy/Fatigue, and 2.8 times more likely to experience improvement in Social Isolation (P<0.05). These quality-of-life improvements are consistent with the improvements in mood measured with the Beck Depression Inventory, the Cornell Dysthymia Rating Scale, and the Profile of Mood States among patients receiving lamotrigine. These data show that lamotrigine monotherapy provides benefits over valproate monotherapy in improving several aspects of health-related quality of life in patients with epilepsy. The observation that quality-of-life improvements during lamotrigine monotherapy occurred concurrently with improvements in mood suggests that the quality-of-life and mood changes may be causally related.
Journal Article↗
Improvement in depression associated with partial epilepsy in patients treated with lamotrigine.
Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Previous studies indicate that lamotrigine may have antidepressant properties. Thirteen adults with uncontrolled partial seizures and concomitant depression were evaluated using measures of depression [Montgomery and Asberg Depression Rating Scale (MADRS) and the MMPI Depression Scale] and anxiety [Spielberger's State-Trait Anxiety Inventory (STAI)] to test the effects of lamotrigine on mood. Evaluations after 5 weeks and again after 3 months of lamotrigine treatment demonstrated significant improvement in depression and anxiety. Mean MADRS overall scores were significantly lower than pretreatment baseline at the 5-week and 3-month evaluations. The mean MMPI Depression score was significantly lower than baseline at the 3-month evaluation. State anxiety scores were significantly reduced from baseline after 5 weeks, but not at 3 months, whereas Trait anxiety scores were reduced from baseline at the 5-week and 3-month evaluations.
Journal Article↗
Occurrence of psychosis in patients with epilepsy randomized to tiagabine or placebo treatment.
PURPOSE: Patients with drug-resistant epilepsy have a higher incidence of psychiatric problems and possibly greater intolerance to antiepileptic drugs (AEDs) than do other patients with epilepsy. Concern has been raised that gamma-aminobutyric acid (GABA)ergic drugs may be associated with treatment-emergent psychosis. Tiagabine (TGB; Gabitril), a new AED that blocks synaptic GABA uptake, was developed in trials of drug-resistant patients with epilepsy. We conducted ad hoc analyses of adverse events, drug intolerance, and treatment response to evaluate the association between TGB treatment and psychosis and whether psychiatric history might be predictive of tolerance or effectiveness of this GABAergic drug. METHODS: Data were analyzed from two multicenter, randomized, double-blind, placebo-controlled trials of add-on TGB therapy (32 or 56 mg daily) in 554 adolescents and adults with complex partial seizures (CPSs). After an 8- or 12-week baseline phase, double-blind treatment consisted of a 4-week titration period (with TGB dose gradually increased to 32 or 56 mg daily) and an 8- or 12-week fixed-dose period. Adverse events commonly associated with psychosis were evaluated. Treatment intolerance and effectiveness (> or =50% reduction in CPS rate) were compared among patients with and without psychiatric histories. RESULTS: Psychotic symptoms (hallucinations) were observed in three (0.8%) of 356 TGB-treated patients and none of 198 placebo-treated patients (p = 0.556, NS). Statistical analysis showed no interaction between psychiatric history and drug intolerance or treatment outcome. CONCLUSIONS: TGB administration appears to carry no significant increased risk of treatment-emergent psychosis. Psychiatric history was not predictive of the tolerance or effectiveness of the drug.
Adolescent↗
Lamotrigine Monotherapy Improves Depressive Symptoms in Epilepsy: A Double-Blind Comparison with Valproate.
Depressive symptoms are highly prevalent in patients with epilepsy. The antiepileptic drug lamotrigine has been shown to be an effective treatment for the depressive phase of bipolar disorder and to enhance mood and well-being in epilepsy patients. The effects of lamotrigine monotherapy on depressive symptoms in epilepsy have not been evaluated to date in a controlled clinical trial. A recently completed double-blind epilepsy trial comparing the effects of lamotrigine monotherapy and valproate monotherapy on weight change incorporated a battery of standard mood assessments. Mean screening Beck Depression Inventory scores showed that both lamotrigine and valproate groups suffered from mild depression at baseline. Lamotrigine monotherapy was reliably associated with earlier and larger improvements than valproate in mood assessed with the Beck Depression Inventory, the Cornell Dysthymia Rating Scale, and the Profile of Mood States. Considered in the context of other data showing lamotrigine's antidepressant efficacy in bipolar depression, these results suggest that lamotrigine improves mood in mildly depressed patients with epilepsy. Lamotrigine may be particularly useful in treating epilepsy patients with comorbid depression, the most common psychiatric illness in epilepsy.
Journal Article↗