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Objective: Rasmussen encephalitis (RE) is a progressive and destructive inflammatory disease of one hemisphere. Its cause is unknown. We investigated comorbidity and laterality factors that might predispose to RE. Methods: We retrospectively compared the histories of 160 RE patients to those with genetic generalized epilepsy (n = 154) and those with focal cortical dysplasia Type II (FCD II; n = 148). Results: The median/mean age at symptom onset in RE was 7/10 years (range = 1–53 years), and 58.1% of the patients were female. The female sex predominated in RE patients, with age > 7 years at disease manifestation. The left hemisphere was affected in 65.6%. Perinatal complications (preterm birth, twin pregnancies, early acquired brain lesions) were more frequent in RE than in control patients. Ipsilateral facial autoimmune conditions (scleroderma en coup de sabre, uveitis, or chorioretinitis) were only observed in RE patients (6.9%). Onset of RE was more frequently associated with fever than that of FCD II. In 33.1% of RE patients, ≥1 potential risk factor was found. Interestingly, 11.9% of patients had one‐sided early brain lesions or facial autoimmune lesions ipsilateral to subsequent RE; none had such a lesion contralaterally. Significance: Perinatal complications and facial autoimmune conditions may act as predisposing factors for RE. Fever might trigger RE manifestation. Further genetic or infectious contributors may be identified in the future. Single or combined hits may be required to elicit or facilitate the start of the disease. Ipsilateral early comorbid lesions or facial autoimmune processes might in part explain the enigmatic unilaterality of RE. [ABSTRACT FROM AUTHOR]

Epileptic seizures vary greatly in clinical phenomenology and can markedly affect the patient's quality of life. As therapeutic interventions focus on reduction or elimination of seizures, the accurate documentation of seizure occurrence is essential. However, patient self-evaluation compared with objective evaluation by video-electroencephalography (EEG) monitoring or long-term ambulatory EEG revealed that patients document fewer than 50% of their seizures, on average, and that documentation accuracy varies significantly over time. For good clinical practice in epilepsy, novel and feasible seizure detection techniques for ambulatory long-term use are needed. Generalised tonic-clonic seizures can already be detected reliably by methods that rely on motion recording (eg, surface electromyography). However, the automatic detection of other seizure types, such as complex partial seizures, will require multimodal approaches that combine the measurement of ictal autonomic alterations (eg, heart rate) and of characteristic movement patterns (eg, accelerometry). Innovative and feasible tools for automatic seizure detection are likely to advance both monitoring of the outcome of a treatment in a patient and clinical research in epilepsy. [ABSTRACT FROM AUTHOR]

The liver toxicity of valproic acid (VPA) is an established side effect of this widely used antiepileptic drug, which is extremely problematic for patients with metabolic epilepsy and particularly epilepsy due to mitochondrial dysfunction. In the present report, we investigated the reason for liver mitochondrial toxicity of VPA and several acid and amide VPA analogues. While the pyruvate and 2-oxoglutarate oxidation rates of rat brain mitochondria were nearly unaffected by VPA, rat liver mitochondrial pyruvate and 2-oxoglutarate oxidation was severely impaired by VPA concentrations above 100 μM. Among the reactions involved in pyruvate oxidation, pyruvate transport and dehydrogenation steps were not affected by VPA, while α-lipoamide dehydrogenase was strongly inhibited. Strong inhibition of α-lipoamide dehydrogenase was also noted for the VPA one-carbon homolog sec-butylpropylacetic acid (SPA) and to a lesser extent for the VPA constitutional isomer valnoctic acid (VCA), while the corresponding amides of the above three acids valpromide (VPD), sec-butylpropylacetamide (SPD) and valnoctamide (VCD) showed only small effects. We conclude that the active inhibitors of pyruvate and 2-oxoglutarate oxidation are the CoA conjugates of VPA and its acid analogues affecting selectively α-lipoamide dehydrogenase in liver. Amide analogues of VPA, like VCD, show low inhibitory effects on mitochondrial oxidative phosphorylation in the liver, which might be relevant for treatment of patients with mitochondrial epilepsy. [ABSTRACT FROM AUTHOR]

Objectives To evaluate dose-response relationship of BGG492 as add-on therapy to 1-3 antiepileptic drugs in patients with partial-onset seizures and to investigate safety and tolerability of BGG492. Methods This was a 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study (core study) with a 30-week, flexible-dose, open-label extension. In the core study, patients were randomized (1:2) to placebo or BGG492 100 mg t.i.d. in cohort 1, and in cohort 2 patients were randomized (1:4) to placebo or BGG492 150 mg t.i.d. On completion of the core study, eligible patients entered the extension study. Primary outcome measures were total partial seizure frequency per 28 days (core study) and safety and tolerability (extension study). Results Overall, 93 patients were randomized (150 mg [n = 44]; 100 mg [n = 24]; placebo [n = 25]), and 81 (87.1%) completed the core study. Fifty-one patients entered and 43 (84.3%) completed the extension study. In the core study, no statistically significant dose-response trend among the BGG492 treatment groups (100 and 150 mg) was observed at the 4-week double-blind maintenance period (weeks 7-10); however, there was higher percent reduction in total partial seizure frequency in the BGG492 150 mg over placebo groups (37.32%; 95% confidence interval [CI] −18.90, 66.95). Dizziness, somnolence, and fatigue were the most common adverse events ( AEs), higher in the BGG492 150 mg group than in the 100 mg and placebo groups (dizziness: 14 [31.8%] vs. 3 [12.5%] and 1 [4.0%]; somnolence: 7 [15.9%] vs. 1 [4.2%] and 1 [4.0%]; fatigue: 5 [11.4%] vs. 1 [4.2%] and 1 [4.0%]). During the open-label extension study, 39 (76.5%) patients on BGG492 had AEs, and the most commonly experienced AEs were dizziness (14 [27.5%]) and somnolence (9 [17.6%]). Significance There was no significant dose-response trend in the BGG492 treatment groups (100 and 150 mg); however, higher percent reduction over placebo was observed in the BGG492 150 mg group. Safety and tolerability data were consistent with the known safety profile for BGG492, and no new safety risks were identified. [ABSTRACT FROM AUTHOR]

Treatment with enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine (CBZ) can lead to changes in reproductive, endocrine, and lipid parameters, resulting in clinical symptoms for some patients. Previous studies indicate that these changes can be reversed by switching to a nonenzyme-inducing AED. Lacosamide is a newer-generation AED, not known to induce or strongly inhibit cytochrome P450 (CYP450) enzymes. In this phase IIIb, prospective, multicenter, open-label, single-arm trial ( NCT01375374 ), the serum concentrations of CYP-related reproductive hormones, thyroid hormones, and lipids were assessed in otherwise healthy male patients with focal seizures (N = 11), before and after a switch from CBZ (600–1200 mg/day at baseline) to lacosamide (target dose: 400 mg/day by the end of titration) as adjunctive treatment to the nonenzyme-inducing AED levetiracetam (LEV, stable dosage of > 1000 mg/day throughout). Cross titration took place over 4 weeks, followed by an 8-week maintenance period. Serum measurements were conducted at baseline and at the end of maintenance. The median serum sex-hormone-binding globulin (SHBG) concentration was towards the higher end of the normal range at baseline and decreased following the switch (61.7 to 47.5 nmol/L, N = 10, p = 0.027 by Wilcoxon signed-rank test). Free androgen index (100 × testosterone/SHBG) and free thyroxine serum concentration increased (25.4 to 36.4 and 13.0 to 14.9 pmol/L, respectively, both N = 10 and p = 0.002). At baseline, the median progesterone serum concentration was below the normal range (0.7 nmol/L), whereas median cholesterol and low-density lipoprotein concentrations were above the normal range (5.5 and 3.6 mmol/L, respectively). By the end of maintenance, all measured parameters were within the normal range. The safety and tolerability profile of lacosamide was consistent with that observed in previous studies. Furthermore, antiseizure efficacy appeared to be maintained, suggesting that deinduction of CYP enzymes following a switch from CBZ to lacosamide as adjunctive therapy to LEV is feasible within 8 weeks and is associated with normalization of serum parameters. [ABSTRACT FROM AUTHOR]

Epilepsy surgery is currently the only way to cure drug-resistant epilepsy (DRE). The loss of epileptic activity or its propagation in the developing brain may not only result in seizure freedom but also be associated with further positive effects. Here, we analyzed the cognitive development of children and adolescents with DRE after epilepsy surgery. We evaluated retrospectively the cognitive development of children and adolescents before and after epilepsy surgery. Fifty-three children and adolescents underwent epilepsy surgery at a median age of 7.62 years. Overall seizure freedom was 86.8% at a current median observation period of 20 months. Presurgically, 81.1% had the clinical diagnosis of cognitive impairment, which was confirmed by standardized tests in 43 of 53 patients (76.7%). Further 10 patients had severe cognitive impairment rendering a standardized test impossible. The median intelligence quotient (IQ)/development quotient value was 74. After surgery, caretakers reported developmental progress in all patients, whereas the median IQ decreased slightly (P = 0.404). In eight patients the IQ points decreased after surgery; however, their individual raw scores increased in line with their reported increase in cognitive abilities. We did not detect any cognitive deterioration in children following epilepsy surgery. A loss of IQ points did not correspond to a real loss of cognitive abilities. These patients developed more slowly than age-matched peers with an average development speed but profited individually as seen in their raw scores. Therefore, an individual analysis of raw scores is relevant to assess the cognitive development after surgery. [ABSTRACT FROM AUTHOR]

Objective: Some patients unexpectedly display an unfavorable cognitive course after epilepsy surgery subsequent to any direct cognitive sequelae of the surgical treatment. Therefore, we conducted in‐depth neuropathological examinations of resective specimens from corresponding patients to provide insights as to the underlying disease processes. Methods: In this study, cases with significant cognitive deterioration following a previous postoperative assessment were extracted from the neuropsychological database of a longstanding epilepsy surgical program. An extensive reanalysis of available specimens was performed using current, state‐of‐the‐art neuropathological examinations. Patients without cognitive deterioration but matched in regard to basic pathologies served as controls. Results: Among the 355 operated patients who had undergone more than one postoperative neuropsychological examination, 30 (8%) showed significant cognitive decline in the period after surgery. Of the 24 patients with available specimens, 71% displayed further neuropathological changes in addition to the typical spectrum (ie, hippocampal sclerosis, focal cortical dysplasias, vascular lesions, and low‐grade tumors), indicating (1) a secondary, putatively epilepsy‐independent neurodegenerative disease process; (2) limbic inflammation; or (3) the enigmatic pathology pattern of "hippocampal gliosis" without segmental neurodegeneration. In the controls, the matched individual principal epilepsy‐associated pathologies were not found in combination with the secondary pathology patterns of the study group. Interpretation: Our findings indicate that patients who unexpectedly displayed unfavorable cognitive development beyond any direct surgical effects show rare and very particular pathogenetic causes or parallel, presumably independent, neurodegenerative alterations. A multicenter collection of such cases would be appreciated to discern presurgical biomarkers that help with surgical decision‐making. ANN NEUROL 2023;93:536–550 [ABSTRACT FROM AUTHOR]

Depression is a serious and frequent comorbidity of epilepsy and other neurological conditions. Here, we review recent studies on the relationship between epilepsy and depression with regard to diagnostic criteria, epidemiology, etiology and treatment. Depression in epilepsy can be described in the general framework of the diathesis-stress model: chronic stress exposure owing to the 'burden of epilepsy' and learned helplessness due to the threat of recurrent seizures as unpredictable aversive events represent psychological risk factors for the development of depression. Epilepsy-related factors (for example, focus site or side) have shown little effect on mood. Nonepileptic individuals who are adversely affected by seizures (for example, parents of pediatric patients with epilepsy, and patients with psychogenic nonepileptic seizures) show increased levels of depression, similar to patients with epilepsy. However, seizures, subclinical hypersynchronous neural discharges and some antiepileptic drugs may cause acute states of depressive mood or depression on a purely neurobiological basis. Antidepressant drugs and psychotherapy have shown moderate efficacy in the treatment of depression comorbidity, but randomized controlled trials in patients with epilepsy are lacking, especially for drugs. [ABSTRACT FROM AUTHOR]

We investigate the influence of various pathophysiologic and physiologic processes on global statistical properties of epileptic brain networks. We construct binary functional networks from long-term, multichannel electroencephalographic data recorded from 13 epilepsy patients, and the average shortest path length and the clustering coefficient serve as global statistical network characteristics. For time-resolved estimates of these characteristics we observe large fluctuations over time, however, with some periodic temporal structure. These fluctuations can-to a large extent-be attributed to daily rhythms while relevant aspects of the epileptic process contribute only marginally. Particularly, we could not observe clear cut changes in network states that can be regarded as predictive of an impending seizure. Our findings are of particular relevance for studies aiming at an improved understanding of the epileptic process with graph-theoretical approaches. [ABSTRACT FROM AUTHOR]

Summary: Objective: To assess the efficacy, safety, tolerability, and pharmacokinetics of adjunctive rufinamide in adults and adolescents with inadequately controlled partial seizures receiving treatment with one to three concomitant antiepileptic drugs (AEDs). Methods: A 24-week multicenter Phase II clinical study was conducted (n =647), comprising a 12-week prospective baseline phase and a 12-week randomized double-blind, parallel-group, five-arm (placebo and rufinamide 200, 400, 800, and 1600mg/day) treatment phase. Results: The linear trend of dose response for seizure frequency per 28 days in the double-blind treatment phase – the primary efficacy outcome measure – was statistically significant in favor of rufinamide (estimated slope=−0.049, P =0.003; minimally efficacious dose, 400mg/day). Response rates, defined as a ≥50% reduction in seizure frequency per 28 days, also revealed a significant linear trend of dose response (P =0.0019, logistic regression analysis). Adverse events were comparable between placebo and all rufinamide groups except the 1600mg/day group; no safety signals were observed. Conclusions: These results suggest that in the dose range of 400–1600mg/day, add-on rufinamide therapy may benefit patients with inadequately controlled partial seizures and is generally well tolerated. These data also suggest that higher doses may confer additional efficacy without adversely affecting safety and tolerability. [Copyright &y& Elsevier]

Diagnosis and management of epilepsy remain challenging, particularly among women of child-bearing age. In 2015, notable steps were taken in the right direction, with w ork that provided insight into the diagnosis of epilepsy, management of this condition during pregnancy, and new treatment options. [ABSTRACT FROM AUTHOR]

Summary: Analysis of ictal semiology is essential to presurgical evaluation of epilepsy patients providing information on seizure origin. To assess the significance of hypersalivation and postictal coughing for seizure origin in temporal lobe epilepsy (TLE), we analyzed video/EEG monitoring documented seizures of 107 adult patients for these seizure elements with respect to frequency and sequence of occurrence in relation to epileptogenic origin, comparing mesial versus extra-mesial and left versus right. Hypersalivation was rare, but occurred exclusively in seizures of mesial origin (9.4%). Comparison between left (11.4%) and right (6.9%) mesial origin was statistically insignificant. Postictal coughing also occurred exclusively in seizures of mesial onset (6.3%). Again, comparison between left (5.7%) and right (6.9%) mesial seizure onset was statistically insignificant. Thus, hypersalivation and postictal coughing are rare seizure phenomena in TLE, but their occurrence strongly support mesial seizure origin. [Copyright &y& Elsevier]

Abstract: The role of neuroscience for the understanding of cognitive processes is a matter of controversial discussions. While it is widely accepted that neuroscientific data do contribute to theories on cognition in some way, their specific value is most often not explicitly described. One central issue is the validity of the inference from neuroscientific data to underlying cognitive processes, which depends on the characteristic properties of the respective neuroscientific method. In the first part of this review, we discuss the conditions under which data from functional MRI (fMRI), surface EEG, and intracranial EEG recordings may be interpreted with respect to associated cognitive processes. We will show that due to the different signal characteristics in each domain, cognitive processes at different levels can be captured. In the second part, we address the specific contribution made by neuroscientific data to the understanding of cognition. We show that neuroscientific findings may move beyond psychological theories based on purely behavioral data in several respects, which again depend on the imaging modality. Taken together, we suggest that neuroscientific data contribute to the understanding of cognition by adding specific biological constraints and by extending the explanatory potential of psychological theories. [Copyright &y& Elsevier]

Electroencephalogram oscillations recorded both within and over the medial frontal cortex have been linked to a range of cognitive functions, including positive and negative feedback processing. Medial frontal oscillatory characteristics during decision making remain largely unknown. Here, we examined oscillatory activity of the human medial frontal cortex recorded while subjects played a competitive decision-making game. Distinct patterns of power and cross-trial phase coherence in multiple frequency bands were observed during different decision-related processes (e.g., feedback anticipation vs. feedback processing). Decision and feedback processing were accompanied by a broadband increase in cross-trial phase coherence at around 220 msec, and dynamic fluctuations in power. Feedback anticipation was accompanied by a shift in the power spectrum from relatively lower (delta and theta) to higher (alpha and beta) power. Power and cross-trial phase coherence were greater following losses compared to wins in theta, alpha, and beta frequency bands, but were greater following wins compared to losses in the delta band. Finally, we found that oscillation power in alpha and beta frequency bands were synchronized with the phase of delta and theta oscillations (''phase-amplitude coupling''). This synchronization differed between losses and wins, suggesting that phase--amplitude coupling might reflect a mechanism of feedback valence coding in the medial frontal cortex. Our findings link medial frontal oscillations to decision making, with relations among activity in different frequency bands suggesting a phase-utilizing coding of feedback valence information. [ABSTRACT FROM AUTHOR]

Abstract: Gray matter heterotopia are a common cause of pharmacoresistant epilepsy. Recently, several case studies have addressed the question of whether heterotopia can contribute to physiological cerebral functions. We describe two cases that demonstrate a functional role for periventricular heterotopia in higher cognitive processes. During presurgical diagnostics, two patients underwent electric stimulation of both the periventricular heterotopia and the overlying cortex. This revealed a functional role of periventricular heterotopia in higher cerebral functions such as language and complex visual and acoustic processing. Furthermore, stimulation of the overlying cortex led to unusually intense positive phenomena, including complex acoustic and gustatory hallucinations and language production. These cases illustrate that periventricular heterotopic neurons can contribute to higher cerebral functions. Interestingly, the anterior-to-posterior representation of these functions is comparable to the normal anterior-to-posterior representation in a normal neocortex (similar to a periventricular “minicortex” in early developmental stages). [Copyright &y& Elsevier]

Previous findings indicate that the hippocampus does not only play a role in long-term memory (LTM) encoding, but is important for working memory (WM) as well, in particular when multiple items are being processed. A recent study showed that maintenance of multiple items was associated with hippocampal activation (hippocampus-dependent WM), while maintenance of individual items induced hippocampal deactivations (hippocampus-independent WM). Here, we used two complimentary approaches to investigate whether WM-related activity patterns occur also during LTM encoding of sequentially presented items and whether they are related to the primacy effect, i.e., improved LTM encoding of items presented at the beginning of the list. Intracranial electroencephalogram in epilepsy patients and functional MRI in healthy subjects were recorded during a word-list learning task. As expected, the proportion of successfully encoded items was higher at the beginning of the list than at later list positions. Items at the beginning of the list which were subsequently forgotten were associated with negative blood oxygen level dependent responses and positive direct current slopes, corresponding to hippocampal deactivations, suggesting that they were not processed in hippocampus-dependent WM. These deactivations were absent for items later in the list and for subsequently remembered items. These data show that if processing of items at the beginning of the list is accompanied by hippocampal activity patterns previously observed during hippocampus-dependent WM, these items are subsequently remembered. However, deactivations of the hippocampus as previously observed during WM maintenance of individual items predicts failure of LTM encoding. [ABSTRACT FROM AUTHOR]

Abstract: There is no reasonable doubt that the hippocampus plays an important role in memory processing. A virtually uncountable number of studies in animals and humans have revealed changes in neural activity in this structure during memory formation [Squire LR. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev 1992;99:195–231; Squire LR, Stark CE, Clark RE. The medial temporal lobe. Annu Rev Neurosci 2004;27:279–306], and hippocampal damage reliably leads to impairments in a large number of memory tests. However, while several correlates of successful memory formation have been found in the hippocampus, it is still an open question why specific neural processes support encoding of a particular item. An answer to this question would help to resolve current debates about which memory functions are actually supported by the hippocampus, and why activity in the neural networks of the hippocampus is involved in, or even necessary for, some memory processes but not for others. In this review, we first summarize findings on the electrophysiological activity within the hippocampus during different memory processes. We try to differentiate whether the hippocampus is merely involved in these processes, or whether the hippocampus appears to be necessary for them. Based on a distinction between a more general “encoding state” and the more specific process of “content-specific memory formation”, we review data on neural representations within hippocampus and neocortex. We suggest that during memory formation, the hippocampus renders neural representations more sparse by providing an inhibitory signal to the neocortex. [Copyright &y& Elsevier]

Abstract: The epilepsies are among the most common serious brain disorders, can occur at all ages, and are characterized by a variety of presentations and causes. Diagnosis of epilepsy remains clinical, and neurophysiological investigations support the diagnosis of the syndrome. Brain imaging is able to identify many of the structural causes of the epilepsies. Current antiepileptic drugs (AEDs) block seizures without influencing the underlying tendency to generate seizures, and are effective in 60–70% of individuals. Several modern drugs are as efficacious as the older medications, but have important advantages including the absence of adverse drug interactions and hypersensitivity reactions. Epilepsy is associated with an increased prevalence of mental health disorders including anxiety, depression, and suicidal thoughts. An understanding of the psychiatric correlates of epilepsy is important to the adequate management of people with epilepsy. Anticipation of common errors in the diagnosis and management of epilepsy is important. Frequent early diagnostic errors include nonepileptic psychogenic seizures, syncope with myoclonus, restless legs syndrome, and REM behavioral disorders, the last mostly in elderly men. Overtreatment with too rapid titration and too high doses or too many AEDs should be avoided. For people with refractory focal epilepsy, vagus nerve stimulation offers palliative treatment with possible mood improvement and neurosurgical resection offers the possibility of a life-changing cure. Potential advances in the management of epilepsy are briefly discussed. This short review summarizes the authors’ how-to-do approach to the modern management of people with epilepsy. [Copyright &y& Elsevier]

Abstract: Flexibly adapting behavior in dynamic environments relies on fronto-limbic networks that include the amygdala, orbitofrontal cortex, and striatum. Animal work demonstrates that interactions among these regions are critical for flexible feedback-guided learning, but it remains unknown to what extent such anatomical–functional interactions operate in humans. Here, we use connectivity analyses in both structural and functional MRI to further our understanding of how brain circuits work in conjunction to promote goal-directed behavior. In particular, fiber tracking based on diffusion-weighted imaging provides information about anatomical connectivity between brain structures, and functional MRI provides estimates of functional connectivity between structures. We found that, during a feedback-guided reversal learning task, the strength of estimated white matter tracts from the amygdala to the hippocampus, orbitofrontal cortex, and ventral striatum predicted both how subjects adapted their behavior following positive and negative feedback, and the functional connectivity (estimated from functional MRI time series) between the amygdala and these regions. In addition, we identified a dissociation between an amygdala-hippocampus circuit that predicted response switching, and an amygdala-orbitofrontal cortex circuit that predicted learning following rule reversals. These findings provide novel insights into how the anatomy and functioning of amygdala-related brain circuits mediate different aspects of feedback-guided learning behavior. [Copyright &y& Elsevier]

In temporal lobe epilepsy, long-term memory disturbance starts early in life mainly affecting declarative memory. Primary impairment of episodic memory often results in reduced semantic and autobiographic memory. Neuropsychological performance predicts academic achievement and everyday life functioning while subjective memory complaints are highly correlated with depression. Memory impairment is also influenced by initial brain damage, developmental retardation and dynamic factors (e.g., seizure frequency, medication). Damage of functional tissue, low mental reserve capacity, and poor seizure outcome increase the risk for postsurgical memory impairment whereas functional release due to seizure freedom counteracts negative impact. Preliminary findings indicate that postsurgical training improves memory deficits and encourage further research. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To assess whether EEG synchronization changes during short-term low-frequency electrical stimulation of the seizure onset zone. Methods: In 10 patients (34±11 years) with pharmaco-resistant epilepsy the seizure onset zone (9 temporal lobe, 1 frontal lobe) was electrically stimulated at 1Hz for 5min via intracranial electrodes. Bipolar stimuli were applied and four pulse widths (0.05, 0.1, 0.5, and 1.0ms) were tested. Stimulation amplitudes were held fixed at 1mA for strip electrodes and at 2mA for depth electrodes. Changes of EEG synchronization were assessed by the eigenvalue dynamics of the cross-correlation matrix computed from a 2.5s sliding window. Results: 37 stimulations were performed. We observed EEG desynchronization in 49% (18/37), an increase of EEG synchronization in 27% (10/37) and an EEG pattern with no significant change of synchronization in 24% (9/37). EEG synchronization most frequently occurred when stimulating with a pulse width of 0.5ms. In a patient with bilateral independent seizure onsets stimulation effects on EEG synchronization were different for each side. In the patient with the shortest duration of temporal lobe epilepsy, stimulation triggered periodic epileptic spikes phase-locked to stimulation. One patient experienced an aura during stimulation, which did not evolve into a seizure, and in one patient a sub-clincial seizure occurred. Discussion: Low-frequency stimulation of the seizure onset zone is associated with different changes of EEG synchronization and its effects depend on the widths of the stimulation pulses. It may be an appropriate stimulation technique for long-term studies assessing whether synchronized or desynchronized brain dynamics prevent seizure occurrence. [Copyright &y& Elsevier]

Background: The diagnosis of nonconvulsive status epilepticus (NCSE) is particularly challenging in elderly patients. Confusion, personality change, dysphasia, subtle motor activity and nystagmus may be the only presenting signs. Objective: To review current knowledge about NCSE with special focus on older people. Methods: Systematic review of the current literature via Medline search. Conclusion: Although prospective studies are still lacking, NCSE may be one of the most frequently missed diagnoses in patients presenting with altered mental status. Elderly patients are at particular risk of diagnostic errors because of the broad range of presentations of NCSE, significant comorbidities (especially cerebrovascular disease), limited awareness of this particular seizure emergency or difficulties with access to electroencephalography. Although diagnostic criteria and treatment remain controversial, the diagnosis of NCSE is important because it is potentially reversible. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To test whether increasing synchronization of neuronal activity might be causally related to seizure termination. Methods: Neuronal synchronization was assessed by the relative changes of the eigenvalue spectrum of the equal-time correlation matrix computed from a short window sliding along multi-channel EEGs, recorded with either intracranial or surface electrodes. Results: Synchronization dynamics of six status epilepticus EEG recordings from six patients were assessed. In all six recordings EEG synchronization fluctuated around relatively low levels during ongoing epileptiform activity. Synchronization only persistently increased before, or in one case, at the end of status epilepticus. Ongoing seizure activity stopped without pharmacological intervention in one patient. In four of the five other cases, the persistent increase of synchronization followed administration of anticonvulsant drugs. Conclusions: Our findings support the hypothesis that increasing synchronization of neuronal activity may be considered as an emergent self-regulatory mechanism for seizure termination. Significance: The traditional concept is challenged that increasing neuronal synchronization during epileptic seizures is always pathological and should be suppressed. On the contrary, our findings imply that therapeutic interventions to increase synchronization during seizures might be beneficial. [Copyright &y& Elsevier]

Objective The current histopathological criteria of Rasmussen's encephalitis (RE) include the presence of T-cell-dominated inflammation, microglial activation, neuronal loss, and astrocytic activation. An in vitro study, however, suggested glutamate receptor 3 (GluR3) antibody-mediated astrocytic loss. Therefore, we investigated astrocytic apoptosis and loss in situ. Methods Histochemical, immunohistochemical, terminal deoxynucleotidyltransferase-mediated biotin-dUTP nick end labeling and in situ hybridization techniques were applied to paraffin sections of 20 RE cases, 6 healthy control subjects, and 6 paraneoplastic encephalomyelitis, 10 Ammon's horn sclerosis, and 5 focal cortical dysplasia cases. Results Astrocytic apoptosis and subsequent loss of these cells is a specific feature of RE. Such lesions are not found in the control groups. In RE, astrocytic apoptosis and loss was present both in cortical and in white matter areas. Astrocytes in these tissues showed major histocompatibility complex class I expression. Furthermore, granzyme-B+ lymphocytes were found in close apposition to astrocytes bordering astrocyte-deficient lesions. Granzyme-B+ granules in these lymphocytes were polarized and faced the astrocytic membranes. No evidence was found for an antibody-mediated destruction. Interpretation We suggest a specific attack by cytotoxic T lymphocytes as a possible mechanism responsible for astrocytic degeneration in RE. The loss of astrocytes might play a role in neuronal dysfunction, seizure induction, and enhancement of neuronal cell death. Ann Neurol 2007 [ABSTRACT FROM AUTHOR]

Abstract: Limbic encephalitis (LE) was described in the 1960s as a clinical–pathological syndrome in adults. Initially, the paraneoplastic form was the center of interest. An increasing number of diagnostically valuable autoantibodies in patients’ sera (and cerebrospinal fluid) have been identified. Lately, the impact of non-paraneoplastic LE cases has been acknowledged. In the serum of some of these patients, antibodies against voltage-dependent potassium channels (VGKC antibodies) have been detected. The characteristic MRI course of LE patients has recently been described in detail: hippocampal swelling and T2/FLAIR signal increase are early findings. After a few months, the swelling regresses, followed by hippocampal atrophy with continuous signal increase. A general consensus on formal diagnostic criteria for all LE subsyndromes has not yet been reached. This article proposes such diagnostic criteria and formulates suggestions for treatment. [Copyright &y& Elsevier]

Abstract: The ability to evaluate outcomes of previous decisions is critical to adaptive decision-making. The feedback-related negativity (FRN) is an event-related potential (ERP) modulation that distinguishes losses from wins, but little is known about the effects of outcome probability on these ERP responses. Further, little is known about the frequency characteristics of feedback processing, for example, event-related oscillations and phase synchronizations. Here, we report an EEG experiment designed to address these issues. Subjects engaged in a probabilistic reinforcement learning task in which we manipulated, across blocks, the probability of winning and losing to each of two possible decision options. Behaviorally, all subjects quickly adapted their decision-making to maximize rewards. ERP analyses revealed that the probability of reward modulated neural responses to wins, but not to losses. This was seen both across blocks as well as within blocks, as learning progressed. Frequency decomposition via complex wavelets revealed that EEG responses to losses, compared to wins, were associated with enhanced power and phase coherence in the theta frequency band. As in the ERP analyses, power and phase coherence values following wins but not losses were modulated by reward probability. Some findings between ERP and frequency analyses diverged, suggesting that these analytic approaches provide complementary insights into neural processing. These findings suggest that the neural mechanisms of feedback processing may differ between wins and losses. [Copyright &y& Elsevier]

Purpose: To evaluate pregabalin as add-on therapy for patients with partial seizures administered as fixed dose or as flexible dose adjusted to optimal seizure reduction and tolerability. Methods: Patients receiving antiepileptic drugs (98.8% between 1 and 3 AEDs; 1.2% on more than 3 AEDs) and experiencing ≥4 partial seizures during the 6-week baseline period and no 4-week seizure-free interval were randomized (1:2:2) to placebo (n = 73), pregabalin fixed dose (600 mg/day BID; n = 137), or pregabalin flexible dose (n = 131; 150 and 300 mg/day for 2 weeks each; 450 and 600 mg/day for 4 weeks each, BID) for 12 weeks. Dosage could be adjusted based on tolerability and maintained when a 4-week seizure-free period was achieved. Primary efficacy parameter was reduction in seizure frequency from baseline. Results: Both pregabalin regimens significantly reduced seizure frequency compared with placebo, by 35.4%, for flexible dose (p = 0.0091) and 49.3% for fixed dose (p = 0.0001) versus 10.6% for placebo, and the fixed-dose group was superior to the flexible-dose group (p = 0.0337). Most adverse events were mild or moderate. Discontinuation rates due to adverse events were 6.8% (placebo), 12.2% (pregabalin flexible dose), and 32.8% (pregabalin fixed dose). Patients receiving pregabalin fixed dose discontinued due to adverse event earlier than other groups. Conclusions: Pregabalin administered twice daily, either as fixed (600 mg/day), or as flexible (150–600 mg/day) dose, was highly effective and generally well-tolerated as add-on therapy for partial seizures with or without secondary generalization. Lower incidence of adverse events and discontinuations were achieved in patients receiving pregabalin when dosing was individualized to optimize efficacy and tolerability. [ABSTRACT FROM AUTHOR]

Cognitive profiles in epilepsy are as heterogenous as the epileptic syndromes themselves; causes, topography of epileptogenic areas, pathogenetic mechanisms, and the diverse features characterising the clinical course all contribute to the effect on cognition. Chronic epilepsy generally impairs cognition, but it also induces processes of functional reorganisation and behavioural compensation. In most idiopathic epilepsies, cognition is only mildly deteriorated or even normal by clinical standards. Localisation-related cryptogenic and symptomatic epilepsy disorders are accompanied by focal deficits that mirror the specific functions of the respective areas. Poor cognitive outcome is generally associated with an early onset and a long duration of the disease and with poor seizure control. There is evidence that cognitive functions are already impaired at the onset of the disease, and that the maturation of cognitive functions in children is susceptible to the adverse influence of epilepsy. In adults, cognitive decline progresses very slowly over decades with an age regression similar to that of people without epilepsy. Successful epilepsy surgery can stop or partly reverse the unfavourable cognitive development, but left-temporal resections in particular have a high risk of additional postoperative verbal memory impairment. Cognitive recovery in the adult brain after successful surgery indicates functional compensation and, to some degree, functional reorganisation or a reactivation of functions previously suppressed by influence from distant but connected epileptogenic areas. [Copyright &y& Elsevier]

Oxcarbazepine (OXC, Trileptal) is a modern antiepileptic drug (AED) used as both monotherapy and adjunctive therapy for the treatment of partial seizures with or without secondary generalization in adults and children above 4 years (USA) or 6 years (Europe) of age. Although OXC has been developed through structural variation of carbamazepine (CBZ) with the intent to avoid metabolites causing side effects, significant differences have emerged between the two drugs. The mechanism of action of OXC involves mainly blockade of sodium currents but differs from CBZ by modulating different types of calcium channels. In contrast to CBZ, which is oxidized by the cytochrome P-450 system, OXC undergoes reductive metabolism at its keto moiety to form the monohydroxy derivative (MHD), which is glucuronidated and excreted in the urine. The involvement of the hepatic cytochrome P-450-dependent enzymes in the metabolism of OXC is minimal. Although it does not prevent interaction with oral contraceptives, it explains why OXC can be more effectively combined with other AEDs such as valproate compared with CBZ. Switching from CBZ to OXC normalized CBZ-associated thyroid and sexual hormone abnormalities and pathological lipid values in small patient samples. OXC is often better tolerated than CBZ and causes fewer rashes than CBZ. Add-on or substitution treatment with OXC was effective in controlled trials even when CBZ did not achieve sufficient seizure control. This constitutes compelling clinical evidence that OXC and CBZ are distinctly different medications. From postmarketing experience in over 1,000,000 patient years, OXC had an advantageous risk–benefit balance also in comparison to other new AEDs. OXC should be preferred over CBZ and other older AEDs because of its proven efficacy and excellent side effect profile in children, adolescents, and adults with partial seizures. [Copyright &y& Elsevier]

This retrospective study was conducted to identify cognitive domains affected by topiramate (TPM), and to evaluate the role of blood serum levels of TPM and comedication in the etiology of TPM-induced cognitive impairment.Forty-two patients on AED polytherapy containing topiramate and a random sample of 42 patients with lamotrigine as the corresponding agent underwent extensive neuropsychological testing. Current blood serum levels of TPM were correlated with test scores.Patients on TPM scored significantly worse in phonematic verbal fluency, memory spans, and working memory; language and memory function were not affected per se. In few cognitive domains, serum levels of TPM and performance were correlated before correction for multiple testing. Drug load of additional medication did not account for differences between or within groups.Consistent with previous reports, patients on AED polytherapy including TPM display a cognitive pattern with specific impairment in executive functions. The severity of the cognitive side effects of TPM may be related to dosing to a certain extent, but this relationship may be disclosed only with larger sample sizes. Accordingly, TPM dosage does not appear to be a good indicator of TPM-related cognitive side effects in the individual patient. [Copyright &y& Elsevier]

Multiple studies have established that approximately one third of patients with epilepsy have seizures that cannot be controlled satisfactorily with antiepileptic drugs (AEDs), but the data have not conclusively determined whether pharmacoresistance develops as a result of the disease process or exists at the time of the initial seizure. The mechanism by which it occurs has not been firmly established, although it is believed to be a multifactorial process. Evidence suggests that drug resistance is present in the early stage of the disease, a concept that is potentially beneficial to patients. The rationale for the concept of pharmacoresistance is clear from both a clinical and scientific perspective. Greater emphasis on identifying the AED most suited to the particular patient on the first attempt, when the likelihood of achieving seizure control is greatest, is one possible consequence.

The population incidence of psychogenic nonepileptic seizures (PNES) may be only 4% that of epilepsy, but many patients with PNES have a tendency to seek medical attention, and PNES make up a larger share of the workload of neurologists and emergency and general physicians. Although a great number of publications describe how PNES can be distinguished from epileptic seizures, it usually takes several years to arrive at this diagnosis, and three-quarters of patients (with no additional epilepsy) are treated with anticonvulsants initially. However, the management of PNES as epileptic seizures can lead to significant iatrogenic harm. Moreover, the failure to recognize the psychological cause of the disorder detracts from addressing associated psychopathology and enhances secondary somatization processes. This review provides an overview of studies of the diagnosis, etiology, treatment, and prognosis of PNES. Physicians should always consider PNES in the differential diagnosis of a seizure disorder. If a diagnosis of PNES is possible, or a diagnosis of epilepsy in doubt, a clear diagnostic categorization should be sought. This should involve the assessment of the patient by a physician versed in the diagnosis of seizure disorders and, in many cases, the documentation of a typical seizure by video-EEG. Outcome may be improved if the diagnosis is more actively sought, made earlier, and communicated more convincingly. [Copyright &y& Elsevier]

Rationale: Topiramate (TPM) is a highly effective anticonvulsant drug, but a comparably high rate of cognitive adverse effects have been reported. In this study, we investigated changes in frontal lobe associated cognitive measures after TPM withdrawal in epilepsy patients hospitalized for presurgical evaluation.Methods: Twenty epilepsy patients were administered a brief neuropsychological test battery before and after withdrawal of TPM. Neuropsychological evaluation included a verbal fluency task, verbal (Wechsler’s digits) and spatial spans (Corsi block-tapping) and Trail Making Test (TMT, parts A and B). Median baseline dosage of TPM was 237.5 mg/d, the median retest-interval was 8 days. Results were compared to a matched group of patients, who had been tested and retested before and after reduction of AEDs other than TPM at comparable time intervals.Results: After TPM withdrawal, group performance appeared significantly improved in five of six tests administered. The scores of the control patients remained largely unchanged after drug reduction. After withdrawal, the scores of the TPM group did not differ significantly from the results of the control group whereas pronounced differences had been observed before. Individual improvement became apparent in the majority of patients. Cognitive performance was not correlated to current daily dosages/current blood serum levels of TPM.Conclusion: Withdrawal of TPM causes significant improvement in frontal lobe associated measures like verbal fluency and working memory. As withdrawal was part of the preoperative work-up, and not initiated because of patients’ complaints or hints of intoxication, cognitive impairment due to TPM appears to be easily overlooked and underestimated. [Copyright &y& Elsevier]

This document, published in the Journal of Neurology, explores the use of [18F]DPA-714-PET-MRI as a diagnostic tool for autoimmune limbic encephalitis (ALE) with specific autoantibodies. The study involved two patients with these autoantibodies, and the results showed increased tracer uptake in certain areas of the brain. The study suggests that [18F]DPA-714-PET-MRI could be a valuable tool for diagnosing ALE and assessing the immune response in the brain. However, further research is needed to fully understand its potential for clinical use in ALE. [Extracted from the article]

Brain electrical activity of 16 patients with temporal lobe epilepsy, recorded intracranially during seizure-free intervals as well as during transitions to the seizure state, was analysed using methods derived from the theory of non-linear dynamics. Long-lasting and marked changes towards low-dimensional system states were found to occur specifically up to 25 min prior to epileptic seizures and allow to predict the occurrence of individual seizures in time. These findings reflect a continuous increase in the degree of synchronicity, and thus open a window for the study of mechanisms generating seizures in humans. This offers new possibilities for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: There is ample evidence that side effects of antiepileptic pharmacotherapy negatively affect quality of life, adherence, and long-term retention. The study was set up to evaluate the anticipated tolerance of common side effects provided that a 50% or 100% reduction of seizure frequency would be achieved. An anonymous inquiry in 79 consecutive patients with epilepsy comprised questions regarding the severity of epilepsy/seizures and the perceived impact of seizures and drug treatment on daily functioning and a 10-tiered rating which assesses 11 common behavioral/psychiatric, cognitive, physiological, or physical side effects according to the degree to which they would be tolerated. Least acceptance was evident for psychiatric side effects followed by cognitive, physiological, and physical side effects. Weight gain and tiredness were the most tolerated side effects. The overall low acceptance of negative side effects was slightly higher in the case of a 100% vs. 50% seizure frequency reduction (28% vs. 21% of the maximum toleration score regarding all side effects). Surely, there is a trade-off between the severity of epilepsy, seizure control, and the acceptance of adverse treatment effects. However, the data disclose that psychiatric and cognitive side effects are least accepted. Thus, consideration of individual tolerance and monitoring of side effects in addition to seizures may increase adherence and therapy success. [Copyright &y& Elsevier]

Abstract: Analysis of ictal semiology is essential to presurgical evaluation of patients with epilepsy. To assess the localizing value of behavioral arrest in temporal lobe epilepsy (TLE), we analyzed 107 video/EEG monitoring-documented seizures of 107 adult patients with TLE for a set of defined seizure phenomena with respect to frequency and sequence of occurrence in relation to epileptogenic (mesial vs extramesial, left vs right) origin. Behavioral arrest was observed more frequently in left-sided temporal seizures: 25.7% of left-sided mesial seizures and 25.0% of left-sided extramesial seizures exhibited behavioral arrest, whereas only 3.4% of right-sided mesial seizures and 10.5% of right-sided extramesial seizures were associated with behavioral arrest. In addition, occurence of behavioral arrest within the sequence of seizure phenomena was remarkably consistent, being observed mainly as the first apparent feature of seizure onset. Thus, behavioral arrest is a valuable early indicator of a left-sided temporal epileptogenic focus in adult patients with TLE. [Copyright &y& Elsevier]

Objective: To determine predictors of focal to bilateral tonic‐clonic seizures (FBTCS) during video–electroencephalography (EEG) monitoring (VEM). Methods: All adult patients undergoing presurgical VEM from 2014 to 2015 in the department of epileptology were eligible (N = 229). Those with refractory focal epilepsy and epileptic seizures recorded during VEM were analyzed (N = 188, Group 1). To assess the effects of antiepileptic drug (AED) taper, the total AED load was calculated as the sum of the ratios of prescribed daily dose and defined daily dose of all AEDs per VEM day and was correlated with the occurrence of focal seizures without bilateral tonic‐clonic seizures (FwoBTCS) and FBTCS. To validate the findings, data of patients undergoing VEM in 2004 and 2005 (Group 2, eligible N = 243, analyzed N = 203) were also investigated. Results: In Group 1, 53 patients had FBTCS and 135 patients had exclusively FwoBTCS during VEM. Reduced AED load at seizure onset was the most important modifiable risk factor for FBTCS (receiver‐operating characteristic [ROC]: area under the curve [AUC] = 0.78). Furthermore, the risk of FBTCS varied with the history and frequency of FBTCS prior to VEM. For instance, patients had a 50% risk of FBTCS by reducing the AED load to ~20% when no information about history of FBTCS was taken into account, to ~30% when a positive history of FBTCS was taken into account, and to ~50% when a high frequency of FBTCS prior to VEM was taken into account. These findings were largely replicated in Group 2 (59 patients with FBTCS and 144 exclusively with FwoBTCS). Significance: The risk of FTBCS during VEM depends on the history and frequency of FTBCS prior to VEM and is particularly associated with the extent of AED reduction. Our data underscore the need for appropriate tapering regimens in VEM units. [ABSTRACT FROM AUTHOR]

The article explains the clinical and research context of informed consent in off-label use and informed consent on incapacitated persons. As stated, in clinical context, the physician-patient relationship is aimed at benefiting the individual patient and the treatment does not follow a study protocol, unlike in the research context. Also, in the clinical context, the physician is bound to apply approved labeled and off-label therapy, which is not required in research context.

Introduction Family burden (FB) in pediatric patients with drug-resistant epilepsy (DRE) is significantly higher than that in children with non-DRE. Epilepsy surgery is an established approach to treat DRE, and this study examines the impact of pediatric epilepsy surgery on FB. Methods We retrospectively analyzed data of families and pediatric patients with focal structural DRE treated with epilepsy surgery at our epilepsy center from April 2018 to November 2021. We examined the relationship between cognitive, behavioral, and epilepsy-specific data and the FB measured with the German version of the Impact on Family Scale before and after epilepsy surgery. Results The study cohort included 31 children with DRE at a mean age of 9 years at surgery (range = 0–16) and a mean epilepsy duration of 3 years (range = 0–14). Cognitive impairment correlated with FB in children with DRE prior to surgery. At the last assessment, 14.5 months (mean, range = 6–24) after epilepsy surgery, 87.2% of patients were seizure-free, FB values had decreased by 75.0%, and behavioral problems had decreased by 85,7%. Cognitive functions remained stable following epilepsy surgery. Conclusion In children with DRE, epilepsy surgery reduces FB. Given the considerable impact of families on the development and wellbeing of their children, the impact of epilepsy surgery should be communicated to affected families. [ABSTRACT FROM AUTHOR]

Focal cortical dysplasias (FCDs) are malformations of cortical development and one of the most common pathologies causing pharmacoresistant focal epilepsy. Resective neurosurgery yields high success rates, especially if the full extent of the lesion is correctly identified and completely removed. The visual assessment of magnetic resonance imaging does not pinpoint the FCD in 30%–50% of cases, and half of all patients with FCD are not amenable to epilepsy surgery, partly because the FCD could not be sufficiently localized. Computational approaches to FCD detection are an active area of research, benefitting from advancements in computer vision. Automatic FCD detection is a significant challenge and one of the first clinical grounds where the application of artificial intelligence may translate into an advance for patients' health. The emergence of new methods from the combination of health and computer sciences creates novel challenges. Imaging data need to be organized into structured, well‐annotated datasets and combined with other clinical information, such as histopathological subtypes or neuroimaging characteristics. Algorithmic output, that is, model prediction, requires a technically correct evaluation with adequate metrics that are understandable and usable for clinicians. Publication of code and data is necessary to make research accessible and reproducible. This critical review introduces the field of automatic FCD detection, explaining underlying medical and technical concepts, highlighting its challenges and current limitations, and providing a perspective for a novel research environment. [ABSTRACT FROM AUTHOR]

The article discusses a study on the use of antiepileptic drug treatment and dementia risk factors. Noted is the progressive mental decline in the older people with dementia as well as the risk for higher doses of antiepileptic drugs (AEDs). Information is also provided on the epidemiological study of health care databases from Finland and Germany.

Recording extracellulary from neurons in the brains of animals in vivo is among the most established experimental techniques in neuroscience, and has recently become feasible in humans. Many interesting scientific questions can be addressed only when extracellular recordings last several hours, and when individual neurons are tracked throughout the entire recording. Such questions regard, for example, neuronal mechanisms of learning and memory consolidation, and the generation of epileptic seizures. Several difficulties have so far limited the use of extracellular multi-hour recordings in neuroscience: Datasets become huge, and data are necessarily noisy in clinical recording environments. No methods for spike sorting of such recordings have been available. Spike sorting refers to the process of identifying the contributions of several neurons to the signal recorded in one electrode. To overcome these difficulties, we developed Combinato: a complete data-analysis framework for spike sorting in noisy recordings lasting twelve hours or more. Our framework includes software for artifact rejection, automatic spike sorting, manual optimization, and efficient visualization of results. Our completely automatic framework excels at two tasks: It outperforms existing methods when tested on simulated and real data, and it enables researchers to analyze multi-hour recordings. We evaluated our methods on both short and multi-hour simulated datasets. To evaluate the performance of our methods in an actual neuroscientific experiment, we used data from from neurosurgical patients, recorded in order to identify visually responsive neurons in the medial temporal lobe. These neurons responded to the semantic content, rather than to visual features, of a given stimulus. To test our methods with multi-hour recordings, we made use of neurons in the human medial temporal lobe that respond selectively to the same stimulus in the evening and next morning. [ABSTRACT FROM AUTHOR]

Objective Cardiorespiratory function alterations are commonly observed with epileptic seizures and may lead to syncope and sudden unexpected death in epilepsy ( SUDEP). Although most previous research has focused on controlling heart rate ( HR) and respiration, little is known about seizure-related regulation of systemic blood pressure ( BP). Herein, we have investigated whether the periictal modulation of systemic BP and HR depends on seizure characteristics. Methods Systemic arterial BP, HR, and peripheral capillary oxygen saturation ( SPO2) were continuously and noninvasively monitored using the ccNexfin device in those epilepsy patients undergoing video-electroencephalography ( EEG) telemetry. Data are given as mean ± standard deviation ( SD). Results Forty-five seizures in 37 patients were included. In focal seizures ( FS, n = 35), the mean arterial BP ( MAP) increased by 33 ± 35% and the HR by 53 ± 44%, whereas the SPO2 remained unaltered. The MAP and HR increases were significantly greater in FS with alterations in consciousness than in those without. For those FS that evolved to bilateral convulsive seizures ( BCS, n = 10), all of the ictal recordings were compromised by artifacts. However, 2 min after seizure cessation, the MAP was enhanced by only 16 ± 14% and returned to a baseline slightly below preictal levels after 5 min, whereas the HR was increased by 77 ± 33% and remained elevated throughout the postictal phase. Significance Periictal regulation of systemic BP and HR displays distinct patterns depending on the type of seizure with focal onset. These changes were unrelated to alterations in SPO2. The potential clinical implications of these findings are discussed in the article. [ABSTRACT FROM AUTHOR]