The cenobamate KORK study-A prospective monocenter observational study investigating cenobamate as an adjunctive therapy in refractory epilepsy, with comparisons to historical cohorts treated with add-on lacosamide, perampanel, and brivaracetam.

OBJECTIVE: In Europe, cenobamate has been approved for use as an adjunctive therapy in adult patients with epilepsy (PWE) with focal-onset seizures (FOS) who have not responded satisfactorily to treatment with at least two antiseizure medications (ASMs). Pivotal trials and real-world observational studies have demonstrated a high efficacy of cenobamate, even in very difficult-to-treat epilepsies. Our aim was to investigate the efficacy of add-on cenobamate in adult PWE who were prospectively monitored. We compared these results with those previously obtained for add-on lacosamide, perampanel, and brivaracetam therapy. METHODS: Patients were enrolled from the CENKORK study, which is a prospective, non-interventional, open-label, monocenter cohort study of adult PWE experiencing FOS. The titration of cenobamate was performed according to the guidelines outlined in the summary of product characteristics. The primary outcome measure was the retention rate at 6 months and 1 year. In addition, we assessed seizure-free rates, the proportion of patients achieving at least a 50% seizure reduction, adverse events, and the reasons for treatment discontinuation. These outcome measures were compared with historical controls treated with adjunctive lacosamide, perampanel, or brivaracetam at our center. RESULTS: Between June 2021 and 2022, 172 PWE with ongoing FOS were included. 22 cases were lost to follow-up, leaving 150 cases for the 1-year assessment. The retention rates at 6 months and 1 year were 88.7% and 80%, respectively. Seizure freedom was achieved in 14% of patients at both the 6-month and 1-year marks, while the ≥50% responder rates were 50% and 61%, respectively. The 6-month retention rate was significantly higher in cenobamate than in other ASMs (p < 0.001 for each comparator). Adverse events were significantly more common with perampanel (p < 0.001). SIGNIFICANCE: Add-on cenobamate proved to be particularly efficacious compared to our experience with other recently introduced ASMs. PLAIN LANGUAGE SUMMARY: This observational study was carried out in 172 adult patients with difficult-to-treat epilepsy who were treated with adjunctive cenobamate. After 1 year, the data of 150 patients could be analyzed. Seizure freedom, in the preceding 3 months, was achieved in 14%. The rate of PWE continuing cenobamate was 80%. In our hands, cenobamate showed promising efficacy and tolerability even when compared to other recently introduced antiseizure medications.

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Objective: Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) with ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies suggest high efficacy with unusually high seizure-free rates. The authors sought to investigate the plasma levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. Methods: Blood samples were collected from adult PWEs who were treated with adjunct cenobamate under steady-state conditions. Daily doses, concomitant medications, efficacy, and tolerability were assessed. The plasma cenobamate levels of seizure-free versus non-responding PWEs and between PWEs with and those without clinical adverse events were compared. Results: Samples from 101 PWEs were included. Thirty-six PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. A linear correlation was found between the daily doses (range: 100 mg-400 mg) and the plasma levels (3.8 mg/L-54.6 mg/L). Neither the daily doses nor the plasma levels differed significantly between the investigated subgroups. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Conclusions: To evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful. A general therapeutic range cannot be defined.

Evaluating the Inheritance Risk: Epilepsy Prevalence among Offspring of Adults with Epilepsy in a Tertiary Referral Epilepsy Center.

While significant strides have been made in comprehending the pathophysiology and treatment of epilepsy, further investigation is warranted to elucidate the factors impacting its development and transmission, particularly within familial contexts. This study sought to explore the prevalence and risk factors associated with epilepsy in the offspring of patients with epilepsy who were treated at a tertiary epilepsy center. Adult patients with confirmed epilepsy (PWE) receiving outpatient care were consecutively enrolled, starting from January 2021 to January 2023. Data were recorded for various variables, including age, gender, epilepsy pathophysiology, cognitive impairment, and family history of epilepsy. Descriptive statistics, various statistical tests, and multivariate logistic regression analyses were employed to analyze the data. A total of 1456 PWE were included. Among them, 463 patients (31.8%) had children. Twenty-five patients had offspring diagnosed with epilepsy, representing a prevalence of 5.4%. Analysis of the offspring with epilepsy revealed older ages, a higher proportion of parents with idiopathic epilepsy, and a greater prevalence of a positive family history of epilepsy. Multivariate logistic regression analysis demonstrated a significant association between a family history of epilepsy and increased epilepsy risk in offspring. Genetic syndrome-immanent predisposition, advanced age, and a family history of epilepsy were identified as significant risk factors for epilepsy in offspring by means of this mono-center study.

Psychiatric assessment prior to and after switch from levetiracetam to brivaracetam.

PURPOSE: Brivaracetam is often used as an alternative to levetiracetam in patients with epilepsy (PWE) encountering efficacy issues or adverse events with levetiracetam. This study evaluated the psychological status of PWE who were switched from levetiracetam to brivaracetam due to psychiatric tolerability concerns in comparison to those who remained on levetiracetam. METHODS: We used various psychological assessments including the Symptom Checklist SCL-90-R, the Beck Depression Inventory-II, and the adverse event profile. Eligible participants completed the questionnaires at baseline and again 8 days later. Psychological changes were assessed using standard statistical methods to show differences between a group that immediately switched from levetiracetam to brivaracetam and another group with unchanged levetiracetam. RESULTS: Between May 2020 and May 2021, 63 patients participated in the study, of whom 34 switched from levetiracetam to brivaracetam. At baseline, participants who switched to brivaracetam had fewer antiseizure medications but experienced more monthly seizures. Baseline scores for anxiety (p = 0.020) and psychoticism (p = 0.046) on SCL-90-R in PWE switched to brivaracetam were higher than in the remaining group. In the subsequent assessment, all psychological scores were reduced and were no longer significantly different between both groups. Using multiple regression, initial treatment with a single antiseizure medication and male gender emerged as predictors of psychological improvement. CONCLUSION: Our study found no increased risk of adverse events or psychiatric symptoms after switching from levetiracetam to brivaracetam. Though statistically non-significant, a trend towards improved psychiatric outcomes in the switch group warrants further investigation in future trials with stronger designs for enhanced statistical power.

Critical flicker fusion in patients with epilepsy under antiseizure medication.

OBJECTIVE: Critical flicker frequency (CFF) and flicker frequency (FF) are used as indicators for the neurotoxic adverse events of drugs in pharmacology. In this pilot study, we investigated whether patients with epilepsy (PWE) treated with various antiseizure medications (ASM) had significantly different CFFs compared with healthy controls. In addition, we investigated the appropriateness of CFF as an objective measurement tool in PWE who reported adverse events according to the adverse event profile (AEP). METHODS: Patients receiving regular antiseizure treatment at our center, along with healthy controls, were included in this study. Clinical neurotoxic symptoms, AEP scores, and serum ASM levels were assessed in the PWE group. We used a CFF device that produced a red-black, green-black, blue-black, or white-black flicker. CFF and FF were compared between PWE and healthy controls. In PWE, the correlation of alterations in CFF and FF with AEP results and through ASM serum concentrations was calculated. RESULTS: A total of 33 PWE and 20 healthy controls participated in the study. Except for two light modalities, CFF and FF were significantly reduced in PWE compared with controls. CFF and FF did not differ significantly between PWE with AEP scores >44 points and those with lower scores. CFF and FF levels did not correlate with changes in AEP scores, serum concentrations, or doses. SIGNIFICANCE: CFF and FF distinguished PWE with ASM from healthy controls. No clinically relevant differentiation was detected in the heterogenous PWE group. To investigate whether CFF and FF may serve as subtle indicators of neurotoxicity or specific modes of action, additional studies are needed in more homogenous PWE groups.

Diagnostic Value of Intermittent Photic Stimulation Among Adult Patients in a Tertiary Referral Epilepsy Center: A Retrospective Study.

PURPOSE: Photosensitivity is a phenomenon that may be elicited by standardized intermittent photic stimulation during EEG recording and is detected more frequently in children and adolescents. Nevertheless, at our Epilepsy Center, we routinely assess photosensitivity in all newly referred adult patients. In this investigation, we sought to address the diagnostic yield under the prerequisites described. METHODS: We reanalyzed all routine EEG recordings among referrals to the department of adults during the first six months of 2019, including a simultaneous video that is always coregistered in our center. The prevalence of abnormal findings during photic stimulation was assessed. RESULTS: Intermittent photic stimulation was performed on 344 patients. Photoparoxysmal response were detected in five subjects (1.5%). All patients were female. Four patients were diagnosed with idiopathic generalized epilepsy, and one with Doose syndrome. Photomyogenic responses were recorded in 1.1% and only in patients with psychogenic nonepileptic seizures. In two subjects with psychogenic nonepileptic seizures, the typical seizure was provoked by intermittent photic stimulation (8.7% of all subjects with psychogenic nonepileptic seizures in this cohort). Photoparoxysmal response was not detected in any subject with focal epilepsy, syncope, or other nonepileptic paroxysmal events. In every case of photoparoxysmal responses, increased photosensitivity had already been reported before recording. CONCLUSIONS: In our study, photoparoxysmal responses was a rare phenomenon among adults with a preponderance of females and idiopathic generalized epilepsies. Intermittent photic stimulation may be helpful in provoking typical psychogenic nonepileptic seizures and thus abbreviate the diagnostic process. Provided a careful history, routine intermittent photic stimulation in adults with epilepsy does not appear to be mandatory.

Everolimus in adult tuberous sclerosis complex patients with epilepsy: Too late for success? A retrospective study.

OBJECTIVE: There is evidence that everolimus (EVE) significantly reduces seizure frequency in epilepsy patients with tuberous sclerosis complex (TSC). Given that TSC-related proliferative processes are more dynamic during brain development, seizure outcomes of patients treated with EVE may be age-related and may be less convincing in adult patients. The aim of this study was to assess the effectiveness and the safety profile of EVE in adults in clinical practice. METHODS: We performed a multicenter retrospective chart review of TSC subjects with active epilepsy who started EVE in adulthood (≥18 years of age) at seven German epilepsy centers. The primary endpoint was the retention rate after 6 months. RESULTS: A total of 45 subjects with a mean age of 31.6 ± 11.1 years at EVE start fulfilled the inclusion criteria. Retention rate after 6 months was 98% (43/44 evaluable subjects). Response rate (seizure reduction ≥ 50%) was 33% (14/43 evaluable subjects; four completely seizure-free). We did not find a significant relationship between epilepsy outcome parameters and patient age at EVE start. Adverse events were reported in 19 subjects and were judged to be serious in six patients. Three patients died during the observation period. SIGNIFICANCE: Evidence suggests that EVE is an effective add-on treatment for epilepsy in adult TSC patients, surprisingly without any age limit to individual benefit. A strong age-dependent effect within the period of adulthood seems unlikely. Even if there was no proof of a causal relationship between deaths and EVE intake, patients with EVE should be carefully monitored, especially for infections and stomatitis.

Clinical experience of abrupt discontinuation of perampanel: a case series.

With an elimination half-life of 105 hours, perampanel (PER) allows a once-daily dosing regimen. In pivotal trials, when PER was tapered, it was therefore usually discontinued abruptly. Thus, in our hospital we have always practiced abrupt cessation. In this case series, we investigated how long PER serum concentrations still remain measurable after abrupt discontinuation of PER and whether withdrawal symptoms, such as an increase in seizures or status epilepticus, occur. PER serum levels and the clinical course of 15 adult in-patients were monitored for three weeks based on a retrospective study design following abrupt discontinuation of PER. After one week, PER was still detected in 13 of 15 patients, after two weeks in 10, and after three weeks in three. Neither a severe increase in seizure frequency nor status epilepticus occurred. However, modifications of the concomitant antiseizure drugs were necessary. The abrupt discontinuation of PER leads to a slow decrease in plasma concentration, thus resembling self-evident gradual discontinuation of PER. In some cases, PER may still be measurable and thus clinically active even weeks after its discontinuation. Efficacy and safety of other antiseizure drugs can be estimated appropriately only thereafter.

Is the anticonvulsant activity of levetiracetam dose-dependent?

PURPOSE: Although levetiracetam (LEV) is globally established as a leading antiseizure medication (ASM) it is still a controversial matter whether dose increases correspond with an increased efficacy if LEV in the recommended dose range did not show satisfying efficacy. In our clinical perception we questioned the value of dose increases in such non-responders. METHODS: In this retrospective monocenter study we analyzed the data of adult people with epilepsies (PWE) with focal-onset seizures who had been treated at the department of adults of the Kork Epilepsy Center between 2009 and 2019, who had been on a stable daily LEV dose and in whom LEV was further increased due to further seizures in spite of baseline LEV in a recommended daily dose range. For reasons of data homogeneity, we included only PWE with at least two definite seizures during the hospital stay under the baseline LEV dose who were treated and observed as in-patients after the increase of LEV for a period at least three-fold longer than the baseline interval before. Additional data acquisition comprised clinical data including adverse events, serum concentrations of LEV and other ASMs, and additional laboratory findings. The primary outcome variable was the change of seizure frequency prior to and after the increase of LEV. RESULTS: Out of 518 PWE who had been on LEV during their hospital stay, a total of 61 PWE fulfilled the inclusion criteria. After a gradual dose increment, 91,8 % of PWE showed a reduced seizure frequency, 73,8 % had a reduction of seizures of 50 % or more, and 21,3 % were seizure-free during the observation period. A significant seizure reduction could be shown with a seizure count of 2,5/week prior to the increment and 0,7/week after dose increment (p < 0,00001). Seven PWE reported minor adverse events and ten PWE showed slight laboratory changes (within normal levels). CONCLUSION: Contrary to our long-term clinical impression, LEV dose increments were reasonable and improved the seizure situation in PWE, usually without additional safety hazards.

Visual illustration supporting patient-physician communication in epilepsy: A validation and reliability study of seizure images.

Seizure manifestations may be difficult to describe in words alone. Thus, initially, 24 seizure images were developed to support communication and gain assistance during obtaining the patient's history. Before being used in clinical practice, these seizure images must be investigated for validity and reliability. We tested the images with untrained participants including patients with epilepsy, persons who had witnessed seizures, and participants who had neither had nor witnessed epileptic seizures. The participants filled in a questionnaire evaluating the images twice within 3 days. The participants were asked to choose one of the 2 written descriptions that best matched each seizure image. The validity was assessed using one-proportion z-test. The reliability was assessed by Gwet's AC1. The first analysis showed that the proportion of correctly identified seizure images was higher than 70%, except for 2 images representing dystonia and myoclonus. The dystonia image was modified, and the myoclonus image was removed. In the final evaluation, the seizure images were identified with an overall correctness ratio of 96%. The final AC1 of the seizure images was classified as very high. The final 23 seizure images are proved to be valid and have a high agreement that can be used in clinical practice.

Is brivaracetam-induced elevation of carbamazepine-epoxide levels common and clinically relevant? - A case series.

Brivaracetam (BRV) was recently introduced for the treatment of patients with focal epilepsy. BRV undergoes relatively few interactions, but one of them leads to the elevation of carbamazepine (CBZ)-10,11-CBZ-epoxide (CBZ-E) if BRV is co-administered with CBZ. This interaction has been considered to be clinically negligible. We present a case series of nine patients. In eight of them, levetiracetam (LEV) was switched to BRV. In the remaining case, oxcarbazepine was replaced by CBZ and added to a stable BRV dose. A marked increase of CBZ-E occurred in every case and was associated with clinically relevant symptoms including blurred vision, diplopia, dizziness, or fatigue in three of them. However, in the remaining six, the elevated CBZ-E levels were not associated with any tolerability problems. The importance of CBZ-E for adverse events under CBZ may have been overemphasized in the past and is not clinically impairing in most cases treated with the combination of BRV and CBZ.

Antiepileptic drugs-induced hyponatremia: Review and analysis of 560 hospitalized patients.

Recent evidence suggests that eslicarbazepine acetate (ESL) might be an appropriate alternative to carbamazepine (CBZ) and oxcarbazepine (OXC) due to its better safety profile. Hyponatremia may be one of the limiting safety problems in CBZ and OXC whereas it has been indicated that ESL is less sensitive for the adverse event. Since our clinical experience is different we investigated the incidence of hyponatremia in 560 consecutive adult inpatients treated at our center in 2015 by reviewing their medical records. Only CBZ, OXC and ESL were associated with hyponatremia. The incidence of hyponatremia induced by ESL was not statistically different from that induced by OXC (43% of patients with OXC and 33% with ESL, p > 0.05). Both were associated with hyponatremia more often than CBZ (16%). OXC-induced hyponatremia was dose-related, ESL-induced hyponatremia was not. Furthermore, both OXC- and ESL-induced hyponatremia occurred particularly often in elderly epilepsy patients. Thus, for elderly patients, both OXC and ESL should be considered with caution.

Real-life experience with brivaracetam in 101 patients with difficult-to-treat epilepsy-A monocenter survey.

PURPOSE: To assess the efficiency of brivaracetam under real-world conditions in a tertiary referral epilepsy center. METHODS: We consecutively collected patients treated at our center with brivaracetam (BRV). After a minimum observation period of six months we retrospectively analyzed the efficiency of BRV. RESULTS: Data of 101 patients (mean age 42 years, range 18-81 years, 54 females,) were analyzed. The median number of antiepileptic drugs (AEDs) used prior to BRV was 10 (range 2-18). The initial dose of BRV was at least 50mg per day, the mean maintenance dose at cut-off was 168.6mg (median 200mg, range 50-400mg). Efficacy data were assessed for the last three months or at the time of the last observation carried forward if BRV had been discontinued prematurely. Responder rate was 27.8% (n=28) with 7% seizure-free patients. Adverse events (AEs) occurred in 37 patients (37%). Most frequent AEs were dizziness (16%) and somnolence (11%). Psychiatric adverse events comprised irritability, aggression, depression and psychosis in single cases. Retention rate after six months was 51.5%. Main reason for discontinuation was a lack of efficacy. In 43 cases LEV and BRV were switched. The switch was performed abruptly without complications. In 26 cases (60%) BRV was discontinued and re-switched to LEV within weeks, mainly due to a lack of better efficacy. After the switch from LEV to BRV we even saw an aggravation both of seizure frequency and severity in 5 cases. Retention rate in patients who had not been on LEV was 57%. CONCLUSION: In our hands BRV appeared to be well tolerated and easy to handle. The retention rate was influenced by patients who were switched from LEV and re-switched because BRV was not more efficient. Switching from and re-switching to LEV was easy.

Eyeball Pressure Stimulation Unveils Subtle Autonomic Cardiovascular Dysfunction in Persons with a History of Mild Traumatic Brain Injury.

After mild traumatic brain injury (mTBI), patients have increased long-term mortality rates, persisting even beyond 13 years. Pathophysiology is unclear. Yet, central autonomic network dysfunction may contribute to cardiovascular dysregulation and increased mortality. Purely parasympathetic cardiovascular challenge by eyeball pressure stimulation (EP), might unveil subtle autonomic dysfunction in post-mTBI patients. We investigated whether mild EP shows autonomic cardiovascular dysregulation in post-mTBI patients. In 24 patients (34 ± 12 years; 5-86 months post-injury) and 27 controls (30 ± 11 years), we monitored respiration, electrocardiographic RR intervals (RRI), systolic and diastolic blood pressure (BPsys, BPdia) before and during 2 min of 30 mm Hg EP, applied by an ophthalmologic ocular pressure device (Okulopressor(®)). We calculated spectral powers of RRI in the mainly sympathetic low frequency (LF; 0.04-0.15 Hz) and parasympathetic high frequency (HF; 0.15-0.5 Hz) ranges, and of BP in the sympathetic LF range, the RRI-LF/HF ratio as index of the sympathetic-parasympathetic balance, normalized (nu) RRI-LF- and HF-powers, and LF- and HF-powers after natural logarithmic transformation (ln). Parameters before and during EP in post-mTBI patients and controls were compared by repeated measurement analysis of variance with post hoc analysis (p < 0.05). During EP, BPsys and BPdia increased in post-mTBI patients. Only in controls but not in post-mTBI patients, EP increased RRI-HFnu-powers and decreased RRI-LF-powers, RRI-LFnu-powers, BPsys-LF-powers, BPsys-lnLF-powers and BPdia-lnLF-powers. RRI-LF/HF ratios slightly increased in post-mTBI patients but slightly decreased in controls upon EP. Even with only mild EP, our controls showed normal EP responses and shifted sympathetic-parasympathetic balance towards parasympathetic predominance. In contrast, our post-mTBI patients could not increase parasympathetic heart rate modulation but increased BP upon EP, indicating a paradox sympathetic activation. The findings support the hypothesis that central autonomic dysfunction might contribute to an increased cardiovascular risk, even years after mTBI.

Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing.

BACKGROUND: In multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions. OBJECTIVES: To evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation. METHODS: Before Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing-up, during metronomic deep-breathing, Valsalva-maneuver, and "sustained-handgrip-exercise" in 21 patients with relapsing-remitting MS, and 20 healthy persons. We calculated sympathetic and parasympathetic cardiovascular parameters, including low- (LF) and high-frequency (HF) powers of RRI- and BP-oscillations, RRI-RMSSDs, RRI- and BP-changes during handgrip-exercise, parasympathetic heart-rate-slowing in relation to BP-overshoot after Valsalva-strain-release. We compared values of healthy persons and patients with and without prolonged heart-rate slowing after Fingolimod-initiation (ANOVA; significance: p<0.05). RESULTS: Upon Fingolimod-initiation, 7/21 patients had prolonged HR-slowing. Before Fingolimod, these patients had higher resting BP and higher BP increase during handgrip-exercise than had the other participants (p<0.05). They did not reduce parasympathetic HR-parameters upon standing-up. After Valsalva-strain-release, their parasympathetic HR-slowing in response to BP-overshoot was four times higher than in the other participants (p<0.05). CONCLUSIONS: The autonomic cardiovascular dysfunction in MS-patients with delayed HR-re-acceleration upon Fingolimod-initiation suggests that MS-related central autonomic lesions compromise HR-re-acceleration upon Fingolimod. TRIAL REGISTRATION: German Clinical Trial Register DRKS00004548 http://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do.

Sympathetic cardiovascular hyperactivity precedes brain death.

OBJECTIVE: The time preceding brain death is associated with complex dysregulation including autonomic dysfunction that may compromise organ perfusion, thus inducing final organ failure. In this study, we assessed autonomic function in patients prior to brain death. METHODS: In 5 patients (2 women, median 60 years, age range 52-75 years) with fatal cerebral hemorrhage or stroke and negative prognosis, we monitored RR-intervals (RRI), systolic and diastolic blood pressure (BP), and oxygen saturation. Adjustment of mechanical ventilation remained constant. We assessed autonomic function from spectral powers of RRI and BP in the mainly sympathetic low- (LF, 0.04-0.15 Hz) and parasympathetic high-frequencies (HF, 0.15-0.5 Hz), and calculated the RRI-LF/HF-ratio as index of sympathovagal balance. Three patients required norepinephrine (0.5-1.6 mg/h) for up to 72 h to maintain organ perfusion. Norepinephrine was reduced to 0.2-0.5 mg/h within 2 h before brain death was diagnosed according to the criteria of the German Medical Association. Wilcoxon test compared average values of ten 2-min epochs determined 2-3 h (measurement 1) and 1 h (measurement 2) before brain death. RESULTS: We found higher systolic (127.3 ± 15.9 vs. 159.4 ± 44.8 mmHg) and diastolic BP (60.1 ± 15.6 vs. 74.0 ± 15.2 mmHg), RRI-LF/HF-ratio (1.2 ± 1.6 vs. 3.9 ± 4.0), and BP-LF-powers (2.7 ± 4.8 vs. 23.1 ± 28.3 mmHg²) during measurement 2 than during measurement 1 (p < 0.05). CONCLUSIONS: The increase in BPs, in sympathetically mediated BP-LF-powers, and in the RRI-LF/HF-ratio suggests prominent sympathetic activity shortly before brain death. Prefinal sympathetic hyperactivity might cause final organ failure with catecholamine-induced tissue damage which impedes post-mortem organ transplantation.