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In recent years, the clinical usefulness of the Wada test (WT) has been debated among researchers in the field. Therefore, we aimed to assess its contribution to the prediction of change in verbal learning and verbal memory function after epilepsy surgery. Data from 56 patients with temporal lobe epilepsy who underwent WT and subsequent surgery were analyzed retrospectively. Additionally, a standard neuropsychological assessment evaluating attentional, learning and memory, visuospatial, language, and executive function was performed both before and 12 months after surgery. Hierarchical linear regression analyses were used to determine the incremental value of WT results over socio-demographic, clinical, and neuropsychological characteristics in predicting postsurgical change in patients’ verbal learning and verbal memory function. The incorporation of WT results significantly improved the prediction models of postsurgical change in verbal learning (∆R2 = 0.233, p = .032) and verbal memory function (∆R2 = 0.386, p = .005). Presurgical performance and WT scores accounted for 41.8% of the variance in postsurgical change in verbal learning function, and 51.1% of the variance in postsurgical change in verbal memory function. Our findings confirm that WT results are of significant incremental value for the prediction of postsurgical change in verbal learning and verbal memory function. Thus, the WT contributes to determining the risks of epilepsy surgery and, therefore, remains an important part of the presurgical work-up of selected patients with clear clinical indications.
Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated regarding its therapeutic properties in several several conditions such as epilepsy, migraine and major depressive disorder and was shown to access similar neural pathways as invasive vagus nerve stimulation. While the vagus nerve's role in gut motility is physiologically established, the effect of taVNS has scarcely been investigated in humans and yielded conflicting results. Real-time gastric magnetic resonance imaging (rtMRI) is an established reproducible method to investigate gastric motility non-invasively. Objective: To investigate the influence of taVNS on gastric motility of healthy participants using rtMRI. Methods: We conducted a randomized, double-blind study using high-frequency (HF) stimulation at 25Hz or low-frequency (LF) taVNS at 1Hz after ingestions of a standardized meal in 57 healthy participants. The gastric motility index (GMI) was determined by measuring the amplitude and velocity of the peristaltic waves using rtMRI. Results: After HF taVNS, GMI was significantly higher than after LF stimulation (p = 0.005), which was mainly attributable to a higher amplitude of the peristaltic waves (p = 0.003). Conclusion: We provide evidence that 4-h of taVNS influences gastric motility in healthy human participants for the first time using rtMRI. HF stimulation is associated with higher amplitudes of peristaltic waves in the gastric antrum compared to LF stimulation. Further studies are needed to investigate the effect of different frequencies of taVNS and its therapeutic properties in conditions with impaired gastric motility.
Background: Refractory status epilepticus (RSE) represents a serious medical condition requiring early and targeted therapy. Given the increasing number of elderly or multimorbid patients with a limitation of life-sustaining therapy (LOT) or within a palliative care setting (PCS), guidelines-oriented therapy escalation options for RSE have to be omitted frequently. Objectives: This systematic review sought to summarize the evidence for fourth-line antiseizure drugs (ASDs) and other minimally or non-invasive therapeutic options beyond guideline recommendations in patients with RSE to elaborate on possible treatment options for patients undergoing LOT or in a PCS. Methods: A systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on fourth-line ASDs or other minimally or non-invasive therapeutic options was performed in February and June 2020 using the MEDLINE, EMBASE and Cochrane databases. The search terminology was constructed using the name of the specific ASD or therapy option and the term ‘status epilepticus’ with the use of Boolean operators, e.g. “(brivaracetam) AND (status epilepticus)”. The respective Medical Subject Headings (MeSH) and Emtree terms were used, if available. Results: There is currently no level 1, grade A evidence for the use of ASDs in RSE. The best evidence was found for the use of lacosamide and topiramate (level 3, grade C), followed by brivaracetam, perampanel (each level 4, grade D) and stiripentol, oxcarbazepine and zonisamide (each level 5, grade D). Regarding non-medicinal options, there is little evidence for the use of the ketogenic diet (level 4, grade D) and magnesium sulfate (level 5, grade D) in RSE. The broad use of immunomodulatory or immunosuppressive treatment options in the absence of a presumed autoimmune etiology cannot be recommended; however, if an autoimmune etiology is assumed, steroid pulse, intravenous immunoglobulins and plasma exchange/plasmapheresis should be considered (level 4, grade D). Even if several studies suggested that the use of neurosteroids (level 5, grade D) is beneficial in RSE, the current data situation indicates that there is formal evidence against it. Conclusions: RSE in patients undergoing LOT or in a PCS represents a challenge for modern clinicians and epileptologists. The evidence for the use of ASDs in RSE beyond that in current guidelines is low, but several effective and well-tolerated options are available that should be considered in this patient population. More so than in any other population, advance care planning, advance directives, and medical ethical aspects have to be considered carefully before and during therapy.
Background: The benefit of adjuvant therapy in synovial sarcoma (SS) treatment is under debate. Long-term follow-up data are missing.
Methods: SS patients treated in the consecutive trials CWS-81, CWS-86, CWS-91, CWS-96, CWS-2002-P, and the SoTiSaR-registry till 2013 were analyzed.
Results: Median age of 185 patients was 13.9 years (0.1–56)—with median follow-up of 7.4 years for 163 survivors. Most tumors (76%) were located in extremities. Size was < 3 cm in 58 (31%), 3–5 cm in 59 (32%), 5–10 cm in 42 (23%), and > 10 cm in 13 (7%) (13 missing). In 84 (45%) tumors, first excision was complete (R0 corresponding to IRS-I-group) and in 101 (55%) marginal (R1 corresponding to IRS-II-group). In a subsequent surgical intervention during chemotherapy, R0-status was accomplished in 23 additional IRS-II-group patients with secondary surgery. Radiotherapy was administered to 135 (73%), thereof 62 with R0-status and 67 R1-status (6 missing information). Adjuvant chemotherapy was administered to all but six patients. 5-year event-free (EFS) and overall survival (OS) was 82.9% ± 5.7 (95%CI) and 92.5% ± 3.9. Local and metastatic relapse-free survival was 91.3% ± 4.3 and 92.3% ± 4.1 at 5 years, respectively. In the multivariate analysis, tumor size and no chemotherapy were independently associated with EFS. Size and site were associated with OS. In a detailed analysis of local and metastatic events, tumor size was associated with an independent risk for developing metastases. No independent factor for suffering local recurrence could be identified.
Discussion: Omission of chemotherapy in a non-stratified way seems not justified. Size governs survival due to high linear association with risk of suffering metastatic recurrence in a granular classification.
Objective: To evaluate the incidence and risk factors of generalized convulsive seizure (GCS)-related fractures and injuries during video-EEG monitoring.
Methods: We analyzed all GCSs in patients undergoing video-EEG-monitoring between 2007 and 2019 at epilepsy centers in Frankfurt and Marburg in relation to injuries, falls and accidents associated with GCSs. Data were gathered using video material, EEG material, and a standardized reporting form.
Results: A total of 626 GCSs from 411 patients (mean age: 33.6 years; range 3–74 years; 45.0% female) were analyzed. Severe adverse events (SAEs) such as fractures, joint luxation, corneal erosion, and teeth loosening were observed in 13 patients resulting in a risk of 2.1% per GCS (95% CI 1.2–3.4%) and 3.2% per patient (95% CI 1.8–5.2%). Except for a nasal fracture due to a fall onto the face, no SAEs were caused by falls, and all occurred in patients lying in bed without evidence of external trauma. In seven patients, vertebral body compression fractures were confirmed by imaging. This resulted in a risk of 1.1% per GCS (95% CI 0.5–2.2%) and 1.7% per patient (95% CI 0.8–3.3%). These fractures occurred within the tonic phase of a GCS and were accompanied by a characteristic cracking noise. All affected patients reported back pain spontaneously, and an increase in pain on percussion of the affected spine section.
Conclusions: GCSs are associated with a substantial risk of fractures and shoulder dislocations that are not associated with falls. GCSs accompanied by audible cracking, and resulting in back pain, should prompt clinical and imaging evaluations.
Purpose: Optimization of local therapies in synovial sarcoma (SS) considered unresectable at diagnosis is needed. We evaluated the effects of neoadjuvant versus adjuvant radiation versus surgery only on long-term outcomes.
Methods: Patients with macroscopic SS tumors before chemotherapy (IRS-group-III) in the trials CWS-81, CWS-86, CWS-91, CWS-96, CWS-2002-P and SoTiSaR-registry were analyzed. Local therapies were scheduled after 3 neoadjuvant chemotherapy cycles.
Results: Median age of 145 patients was 14.5 years. 106 survivors had median follow-up of 7.0 years. Tumor site was 96 extremities, 19 head–neck, 16 shoulder/hip, 14 trunk. Tumors were < 3 cm in 16, 3–5 cm in 28, 5–10 cm in 55, > 10 cm in 34 patients. In a secondary resection during chemotherapy, R0-status was accomplished in 82, R1 in 30, R2 in 21 (12 missing). Radiotherapy was administered to 115 (R0 61, R1 29, R2 20, missing 5), thereof 57 before and 52 after tumor resection. 23 were treated with surgery only. For all patients, 5 year event-free (EFS) and overall survival (OS) was 68.9% ± 7.6 (95%CI) and 79.1% ± 6.9. To establish independent significance, tumor site, size, surgical results and sequencing of local therapies were analyzed in a Cox regression analysis. Variables associated with EFS and OS are site, size and sequencing of local therapies. Variables associated with local recurrence are site, surgical results and sequencing of local therapies. The only variable associated with suffering metastatic recurrence is tumor size.
Conclusion: Differences in sequencing of local therapy procedures are independently associated with outcomes. Best local control is achieved when tumors are irradiated pre-operatively and undergo R0 or R1 resection thereafter.
Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus. Translation of these findings would benefit from evidence of efficacy in non-status epilepticus models and validation in another species. Here, we report that electrographic seizures and convulsive behavior are strongly reduced in adult mice pre-treated with Ant-134 in the pentylenetetrazol model. Pre-treatment with Ant-134 did not affect the severity of status epilepticus induced by perforant pathway stimulation in adult rats, a toxin-free model of acquired epilepsy. Nevertheless, Ant-134 post-treatment reduced the number of rats developing spontaneous seizures by 86% in the perforant pathway stimulation model and Ant-134 delayed epileptiform activity in a rat ex vivo hippocampal slice model. The potent anticonvulsant effects of Ant-134 in multiple models may encourage pre-clinical development of this approach to epilepsy therapy.
Background. Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. Methods. We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were estimated using the Kaplan–Meier method. To identify prognostic factors, univariate and multivariate analyses were performed based on Cox regressions. Results. The median age was 67 years (19–72.8 years). Primary sites were cutaneous (27.2%), breast (38.2%), and deep soft tissue (34.6%). The majority was primary angiosarcomas (55.9%) followed by postradiation (40.4%) and chronic lymphedema angiosarcomas (2.9%). Prognosis significantly differed depending on the primary site and etiology. Shortest median OS and MFS were observed in deep soft tissue angiosarcomas, whereas cutaneous angiosarcomas, angiosarcomas of the breast, and radiation-associated angiosarcomas displayed worse median LRFS. Univariate analyses showed better OS for tumor size <10 cm (p = 0.009), negative surgical margins ( = 0.021), and negative lymph node status (p = 0.007). LRFS and MFS were longer for tumor size <10 cm (p = 0.012 and p = 0.013). In multivariate analyses, age <70 years was the only independent positive prognostic factor for OS in all subgroups. For LRFS, secondary AS of the breast was a negative prognostic factor (HR: 2.35; p = 0.035). Conclusions. Different behaviors and prognoses depending on the primary site and etiology should be considered for the treatment of this heterogeneous disease. In cutaneous angiosarcomas of the head/neck and postradiation angiosarcomas of the breast, local recurrence seems to have a crucial impact on OS. Therefore, improved local therapies and local tumor staging may have to be implemented. However, in deep soft tissue angiosarcomas, distant recurrence seems to have a major influence on prognosis, which indicates a benefit of additional perioperative chemotherapy.
Objective: We sought to evaluate the efficacy and tolerability of intranasal midazolam (in‐MDZ) as first‐line inhospital therapy in patients with status epilepticus (SE) during continuous EEG recording.
Methods: Data on medical history, etiology and semiology of SE, anticonvulsive medication usage, efficacy and safety of in‐MDZ were retrospectively reviewed between 2015 and 2018. Time to end of SE regarding the administration of in‐MDZ and ß‐band effects were analyzed on EEG and with frequency analysis.
Results: In total, 42 patients (mean age: 52.7 ± 22.7 years; 23 females) were treated with a median dose of 5 mg of in‐MDZ (range: 2.5–15 mg, mean: 6.4 mg, SD: 2.6) for SE. The majority of the patients suffered from nonconvulsive SE (n = 24; 55.8%). In total, 24 (57.1%) patients were responders, as SE stopped following the administration of in‐MDZ without any other drugs being given. On average, SE ceased on EEG at 05:05 (minutes:seconds) after the application of in‐MDZ (median: 04:56; range: 00:29–14:53; SD:03:13). Frequency analysis showed an increased ß‐band on EEG after the application of in‐MDZ at 04:07 on average (median: 03:50; range: 02:20–05:40; SD: 01:09). Adverse events were recorded in six patients (14.3%), with nasal irritations present in five (11.9%) and prolonged sedation occurring in one (2.6%) patient.
Conclusions: This pharmaco‐EEG–based study showed that in‐MDZ is effective and well‐tolerated for the acute treatment of SE. EEG and clinical effects of in‐MDZ administration occurred within 04:07 and 5:05 on average. Intranasal midazolam appears to be an easily applicable and rapidly effective alternative to buccal or intramuscular application as first‐line treatment if an intravenous route is not available.