Severe memory decline along with unaffected executive functions under 400 mg/day of cenobamate leading to a collapse in school performance.

Cenobamate (CNB) is one of the newer antiseizure medications for the treatment of focal-onset seizures. The cognitive profile of CNB is not yet known in detail. Here we present the case of an 18-year-old male high school student with epilepsy who received adjunctive CNB. Under 400 mg/d of CNB in combination with lamotrigine, a neuropsychological reassessment revealed a severe deterioration of the formerly normal episodic memory functions, while executive functions remained unaffected. The de novo memory deficit had already led to a collapse in school performance and he unexpectedly failed to obtain the general qualification for university entrance. Given the beneficial effect of CNB on seizure control, a dose reduction of CNB to 200 mg/d and introduction of valproic acid was performed. This led to a full recovery of objective memory performance. To our knowledge this is the very first report of a dose-dependent, selective and severe decline in episodic memory performance under CNB, potentially impeding academic achievement. The findings call for a cognitive monitoring of CNB which also addresses episodic memory in addition to executive functions. Systematic studies on episodic memory upon CNB treatment would help to appreciate the scope of this apparently reversible adverse effect.

What Ethics Support for Resolving Ethical Conflicts Do Internists Use in Spanish Hospitals?

Background Ethical conflicts generate difficulties in daily clinical activity. Which methods of ethical advice are most frequently used to resolve them among Spanish doctors has not been studied. The objective of this study is to describe what methods hospital internal medicine physicians in Spain use to resolve their ethical doubts and which they consider most useful. Design A cross-sectional observational study was conducted through a voluntary and anonymous survey and distributed through an ad hoc platform of the Spanish Society of Internal Medicine. Measures We measured methods by which to resolve doubts, types of tools sought, frequency of consulting the Clinical Ethics Committees, and satisfaction with resolution of ethical issues. Results Of 261 internists surveyed, 86 per cent resolve their ethical doubts with assistance, the most frequently used method being consultation with colleagues (58.6 per cent), followed by using specific protocols or guides (11.8 per cent) and consultation with experts in bioethics (9.6 per cent). The most preferred tools are the creation of protocols (30.3 per cent) and the establishment of a consultant/expert in bioethics (27.8 per cent). Conclusions Internists in Spain usually seek assistance to resolve their ethical doubts. Consulting colleagues is the most frequently adopted method. The majority regard tools to resolve ethical conflicts as necessary, seeking above all protocols and consultants/experts in bioethics.

DBS of the ANT for refractory epilepsy: A single center experience of seizure reduction, side effects and neuropsychological outcomes.

Objective: Evaluation of the antiseizure efficacy, side effects and neuropsychological effects of Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT). ANT-DBS is a treatment option for patients with difficult-to-treat epilepsy. Though several works outline the cognitive and/or mood effects of ANT-DBS for the treatment of epilepsy, data on the intersection between antiseizure efficacy, cognitive and undesired effects are scarce. Methods: We retrospectively analyzed the data of our cohort of 13 patients. Post-implantation seizure frequencies were measured at 6 months, 12 months and last follow-up, as well as averaged throughout follow-up. These values were then compared with mean seizure frequencies in the 6 months before implantation. To address acute cognitive effects of DBS a baseline assessment was performed after implantation and before stimulation, and a follow-up assessment was conducted under DBS. The long-term effects of DBS on cognition were assessed by comparing the preoperative neuropsychological profile with a long-term follow-up under DBS. Results: In the entire cohort, 54.5% of patients were responders, with an average seizure reduction of 73.6%. One of these patients achieved temporary seizure freedom and near-total seizure reduction during the entire follow-up. Seizure reduction of <50% was achieved in 3 patients. Non-responders suffered an average seizure increase of 27.3%. Eight of twenty-two active electrodes (36,4%) were off-target. Two of our patients had both electrodes implanted off-target. When removing these two patients from the analysis and averaging seizure frequency during the entire follow-up period, four patients (44.4%) were responders and three experienced a seizure reduction of <50%. Intolerable side effects arose in 5 patients, mostly psychiatric. Regarding acute cognitive effects of DBS, only one patient showed a significant decline in executive functions. Long-term neuropsychological effects included significant intraindividual changes in verbal learning and memory. Figural memory, attention and executive functions, confrontative naming and mental rotation were mostly unchanged, and improved in few cases. Significance: In our cohort, more than half of patients were responders. Psychiatric side effects seem to have been more prevalent compared to other published cohorts. This may be partially explained by a relatively high occurrence of off-target electrodes.

Animating Clinical Ethics: A Structured Method to Teach Ethical Analysis Through Movies.

Movies can serve valuable didactic purposes teaching clinical ethics to medical students. However, using film sequences as means to develop critical thinking is not a straightforward task. There is a significant gap in the literature regarding how to analyse the ethical content embedded in these clips systematically, in a way that facilitates the students' transition from anecdotal reflections to abstract thinking. This article offers a pedagogical proposal to approach the ethical analysis of film sequences in a systematic fashion. This structured stepwise method encourages students to identify the main ethical problem of a selected scene and to reflect on the theoretical principles involved, emphasizing the application of these norms and values in a contextually situated analysis. We believe this method in film studies both reinforces the students' comprehension of the theoretical framework of an ethical topic, and casts light on its pertinence and limitations under the circumstances of the scene, thus proving a constructive tool to strengthen the bridge between the theoretical teaching of clinical ethics and clinical practice.

Anti-seizure efficacy and retention rate of carbamazepine is highly variable in randomized controlled trials: A meta-analysis.

We sought to assess the anti-seizure efficacy of carbamazepine (CBZ) and retention rate (RR) in randomized, controlled trials (RCTs) in epilepsy. Our analysis was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Inclusion criteria were monotherapy of CBZ in adequate dosage for epilepsy treatment and RCT duration of ≥3 months. Outcome measures were seizure freedom rate (SFR) and RR. Random-effects meta-analyses were performed to allow for comparison with other anti-seizure medications (ASMs). Thirty RCTs of 734 were included. SFR at last follow-up ranged from 11% at 36 months to 85% at 3 months. The aggregated SFR at 6 months was 58% (CI 49-66%) and 48% (CI 40-57%) at 12 months. The 6-month SFR among blinded studies was 55% (CI 43-66%), compared with 61% (CI 50-71%) in unblinded studies. The 12-month SFR was not significantly linked to the age of study participants. RR varied from 36% at 24 months to 81% at 6 months. When adjusting for blinding, the aggregated 6-month RR in blinded studies was 59% (CI 52-66%) vs 76% (CI 71-81%) in unblinded studies. The point estimates of SFR of all RCTs showed an upward time trend, with an increase of approximately 15% between the years 1981 and 2018. In conclusion, the SFR and RR of CBZ were highly variable in RCTs and especially affected by study duration and blinding. These results underscore the impact of the design of RCTs investigating ASM and may challenge the wide use of CBZ as a comparator.

Seizure underreporting in LGI1 and CASPR2 antibody encephalitis.

Patients with anti-leucine-rich glioma-inactivated 1 protein (LGI1) or anti-contactin-associated protein 2 (CASPR2) antibody encephalitis typically present with frequent epileptic seizures. The seizures generally respond well to immunosuppressive therapy, and the long-term seizure outcome seems to be favorable. Consequentially, diagnosing acute symptomatic seizures secondary to autoimmune encephalitis instead of autoimmune epilepsy was proposed. However, published data on long-term seizure outcomes in CASPR2 and LGI1 antibody encephalitis are mostly based on patient reports, and seizure underreporting is a recognized issue. Clinical records from our tertiary epilepsy center were screened retrospectively for patients with LGI1 and CASPR2 antibody encephalitis who reported seizure freedom for at least 3 months and received video-electroencephalography (EEG) for >24 h at follow-up visits. Twenty (LGI1, n = 15; CASPR2, n = 5) of 32 patients with LGI1 (n = 24) and CASPR2 (n = 8) antibody encephalitis fulfilled these criteria. We recorded focal aware and impaired awareness seizures in four of these patients (20%) with reported seizure-free intervals ranging from 3 to 27 months. Our results question the favorable seizure outcome in patients with CASPR2 and LGI1 antibody encephalitis and suggest that the proportion of patients who have persistent seizures may be greater. Our findings underline the importance of prolonged video-EEG telemetry in this population.

Operation of a triage committee for advanced life support during the COVID-19 pandemic.

BACKGROUND: During the first weeks of March 2020 in Spain, the cases of severe respiratory failure progressively increased, generating an imbalance between the clinical needs for advanced life support (ALS) measures and the effective availability of ALS resources. To address this problem, the creation of triage committees (TC) was proposed, whose main function is to select the best candidates to receive ALS. The main objective of our study is to describe the clinical characteristics of the patients evaluated by the TC of the Alcorcón Foundation University Hospital (AFUH) during the first wave of SARS CoV-2. Other objectives are to determine if there are differences between the patients considered candidates / not candidates for ALS and to analyze the functioning of the TC. METHODS: Retrospective observational study of all patients assessed by the AFUH TC. RESULTS: There were 19 meetings, in which 181 patients were evaluated, 65.4% male and with a mean age of 70.1 years. 31% had some degree of functional dependence, the Barthel median was 100 and Charlson 4. 58.5% were not considered a candidate for ALS at that time. The patients considered candidates to receive ALS were younger (72 vs 66; p < 0.001), had less comorbidity (Charlson 4 vs 3; p < 0.001) and had a better previous functional situation. A median of 5 physicians participated in each meeting and, after being assessed by the TC, 13.6% received ALS: 29.3% of those considered candidates for ALS and 2% of the non-candidates. CONCLUSIONS: The patients evaluated by the TC had a mean age of 70 years, high comorbidity and almost a third had some degree of functional dependence. More than half were not considered candidates for ALS at that time, these patients being older, with more comorbidity and a worse previous functional situation. TC decisions, based on objective clinical criteria, were almost always respected. Public institutions must get involved in triage procedures, which should and in our opinion must include the creation of TC in health centers. The implementation of Anticipated Decision programs (ADP) would help enable patients affected by triage decisions to participate in them.

Are we creating a new phenotype? Physiological barriers and ethical considerations in the treatment of hereditary transthyretin-amyloidosis.

Hereditary transthyretin (TTR) amyloidosis (ATTRv) is an autosomal dominant, systemic disease transmitted by amyloidogenic mutations in the TTR gene. To prevent the otherwise fatal disease course, TTR stabilizers and mRNA silencing antisense drugs are currently approved treatment options. With 90% of the amyloidogenic protein produced by the liver, disease progression including polyneuropathy and cardiomyopathy, the two most prominent manifestations, can successfully be halted by hepatic drug targeting or-formerly-liver transplantation. Certain TTR variants, however, favor disease manifestations in the central nervous system (CNS) or eyes, which is mostly associated with TTR production in the choroid plexus and retina. These compartments cannot be sufficiently reached by any of the approved medications. From liver-transplanted patients, we have learned that with longer lifespans, such CNS manifestations become more relevant over time, even if the underlying TTR mutation is not primarily associated with such. Are we therefore creating a new phenotype? Prolonging life will most likely lead to a shift in the phenotypic spectrum, enabling manifestations like blindness, dementia, and cerebral hemorrhage to come out of the disease background. To overcome the first therapeutic limitation, the blood-brain barrier, we might be able to learn from other antisense drugs currently being used in research or even being approved for primary neurodegenerative CNS diseases like spinal muscular atrophy or Alzheimer's disease. But what effects will unselective CNS TTR knock-down have considering its role in neuroprotection? A potential approach to overcome this second limitiation might be allele-specific targeting, which is, however, still far from clinical trials. Ethical standpoints underline the need for seamless data collection to enable more evidence-based decisions and for thoughtful consenting in research and clinical practice. We conclude that the current advances in treating ATTRv amyloidosis have become a meaningful example for mechanism-based treatment. With its great success in improving patient life spans, we will still have to face new challenges including shifts in the phenotype spectrum and the ongoing need for improved treatment precision. Further investigation is needed to address these closed barriers and open questions.

Implementation of a telemedicine geriatric co-evaluation in the emergency department: a prospective pilot study.

  INTRODUCTION: Complex drug management is a common challenge in the treatment of geriatric patients. Pandemic scenarios, such as the current one (COVID-19), call for a reduction of face-to-face meetings, especially for elderly patients. Therefore, the aim of the present study was to compare the innovative concept of applying telemedical assessment to geriatric patients in the emergency department (ED) with ED standard treatment. The therapeutic recommendations regarding drug management from the two assessments were compared. A special focus was the use of potentially inadequate drugs (PIMs) for geriatric patients according to the “Fit for the Aged” (FORTA) classification. METHODS: 50 patients (40% female) aged ≥70 years and assessed with an Identification of Seniors at Risk Score (ISAR score) of ≥2 admitted to the ED were prospectively enrolled in this study between November 2017 and February 2018. In addition to the standard treatment in the ED, co-evaluation via video transmission was independently carried out by a board-certified geriatrician. Drug recommendations by ED physicians (A) and the geriatrician (B) were compared. RESULTS: There was a significantly higher frequency of recommendations regarding changes to preexisting medication (p <0.001, n = 50) via geriatric telemedicine in comparison with standard ED treatment. The geriatrician intervened significantly more often than the ED physicians: discontinuation of a drug, p <0.001; start of a new drug, p = 0.004; dose change of a drug, p = 0.001; n = 50). Based on the additional therapy recommendations of the geriatrician, the amount of medication taken by the patient was significantly reduced compared with standard ED treatment (ED assessment t(49) = 0.622 vs geriatrician’s assessment t(49) = 4.165; p <0.001; n = 50). Additionally, the number of PIMs was significantly reduced compared with standard medical treatment (p <0.001). The geriatrician changed 53.9% of the drugs (35/65) whereas the ED physicians changed only 12.3% (8/65). Recommendations for immediate drug therapy, however, were made more frequently by ED physicians (p <0.039, n = 50). DISCUSSION: An early assessment of elderly emergency patients by a geriatrician had a significant impact on the number of drug interventions in the ED. The number of PIMs could be significantly reduced. Whether this also has a positive effect on the further inpatient course needs to be investigated in further prospective studies. The study was retrospectively registered at ClinicalTrials.gov (NCT04148027).  .

Psychological well-being of palliative care professionals: Who cares?

BACKGROUND: Traditionally, the psychological well-being of healthcare workers has been taken for granted - it has even been considered a part of the requirements that were demanded of them. When these professionals have experienced suffering and psychological depletion, they have been held accountable for this suffering, adopting an individualistic and reductionist viewpoint focused only on the professional. This approach has become obsolete due to its proven ineffectiveness, especially from an ethics of responsibility and organization viewpoint. CONTEXT: The psychological well-being of the healthcare worker (and its opposites: suffering, exhaustion, and disenchantment) is advantageous to the professional's commitment to the institution, to their work performance, and to their personal life. OBJECTIVE: The objective of this paper is to reflect on the psychological suffering of the palliative care professional. METHOD: We will reflect on the three levels of responsibility that influence such suffering (micro-meso-macro-ethical; worker-environment-institution). RESULTS: We will propose a global strategy for the care of psychological well-being supported by scientific evidence and key references. SIGNIFICANCE OF RESULTS: We conclude with some contributions on what we have learned and still have to learn on this topic.

The Use of Advance Directives in Specialized Care Units: A Focus Group Study With Healthcare Professionals in Madrid.

Eight focus groups were conducted in four public hospitals in Madrid to explore healthcare professionals' perceptions of advance directives (ADs) in order to improve the understanding of their lack of success among physicians and patients. A purposive sample of sixty healthcare professionals discussed ADs and reasons for their infrequent use. Three main themes were identified: perceptions about their meaning, appraisals of their use in clinical practice, and decision-making about them. Healthcare professionals perceived a lack of clarity about their definition and implementation. There is insufficient awareness of their efficacy in improving the quality of clinical relationships and decision-making, and they are often perceived only as a bureaucratic procedure. Advance directives are not integrated in the clinical practice of Madrid's healthcare specialist services because their application is exceedingly complex, because of insufficient education about them (for both professionals and citizens), and because of lack of procedural clarity. Consequently, healthcare professionals are not aware of how ADs could improve clinical decision-making, of when and for whom their use is appropriate, and of who has responsibility for providing ADs-related information to patients. These circumstances contribute to patients' lack of interest in completing these documents and to physicians' sceptical views about their usefulness.

Gaze Palsy as a Manifestation of Todd's Phenomenon: Case Report and Review of the Literature.

Background: Though Todd's phenomenon (TP) is a relatively rare occurrence, its correct identification is of key diagnostic and therapeutic importance as a stroke mimic. Here we describe a case of isolated gaze palsy as a manifestation of TP, discuss periictal gaze abnormalities as lateralizing sign involving the frontal eye field (FEF), and present a narrative literature review. Methods: We reviewed the main features of the case and conducted a structured literature search of TP and gaze palsy using PubMed. We restricted the search to publications in English, Spanish, French, and German. Case presentation: A 71-year-old male with a history of right frontotemporal subarachnoid hemorrhage was admitted to the Emergency Department of our institution after suffering a first unprovoked focal to bilateral tonic-clonic seizure with ictal gaze deviation to the left. Cranial imaging showed no signs of ischemia, intracerebral hemorrhage, or tumor. The patient presented the following postictal features: involuntary eye deviation to the right due to left-sided gaze palsy and disorientation in time with preserved responsiveness. Eye movements were normal three days later. We concluded that the patient suffered from new-onset epilepsy due to sequelae following the right frontotemporal subarachnoid hemorrhage, affecting the FEF with contralateral ictal gaze deviation, and postictal gaze palsy with ipsilateral eye deviation as an unusual Todd's phenomenon. Conclusion: Unusual manifestations of TP are uncommon but clinically highly relevant, as they can mimic stroke or epileptic status and are decisive in the diagnostic and therapeutic decision-making process. Though postictal gaze palsy has been reported associated with other deficits, this constitutes, to our knowledge, the first report of isolated gaze palsy as a form of TP. Further research into the underlying causes is needed. Ictal contralateral gaze and head deviation, and probably postictal ipsilateral gaze deviation if present, are very helpful for the lateralization of the seizure-onset zone.

The assessment of dermatological emergencies in the emergency department via telemedicine is safe: a prospective pilot study.

The aim of the study was to examine the feasibility and safety of telemedicine for dermatological emergency patients in the emergency department. This observational study was monocentric, open, prospective and two-arm randomized [control group (n = 50) and teledermatology group (n = 50)]. The control group was conventionally recruited directly by a dermatologist. In the teledermatology group patients, images of the skin lesions and clinical parameters were transferred to a tablet PC (personal computer) by an emergency physician and telemedically assessed by a dermatologist without patient contact. Subsequently, the dermatologist, who was previously telemedically contacted, then personally examined the patient in the emergency department. The treatment time between the control group and the teledermatology group was also recorded and compared. The agreement in suspected diagnosis between teledermatological evaluation and clinical evaluation of the same physician in the teledermatology group was 100%. The treatment time [mean (minutes) ± standard deviation] of the control group was 151 ± 71, that of the teledermatology group was 43 ± 38 (p < 0.001). The use of emergency telemedicine is safe and effective and provides a viable alternative for clinical care of emergency patients.

Cardiac stress after electroconvulsive therapy and spontaneous generalized convulsive seizures: A prospective echocardiographic and blood biomarker study.

AIM: Knowledge about cardiac stress related to seizures in electroconvulsive therapy (ECT) and spontaneously occurring generalized convulsive seizures (GCS) is limited. The aim of the present study was to analyze cardiac function and circulating markers of cardiac stress in the early postictal period after ECT and GCS. METHODS: Patients undergoing ECT in the Department of Psychiatry, Psychotherapy and Psychosomatics and patients undergoing diagnostic video-EEG monitoring (VEM) in the Department of Neurology were prospectively enrolled between November 2017 and November 2018. Cardiac function was examined twice using transthoracic echocardiography within 60 min and >4 h after ECT or GCS. Established blood markers (troponin T high-sensitive, N-terminal pro brain natriuretic peptide) of cardiac stress or injury were collected within 30 min, 4 to 6 h, and 24 h after ECT or GCS. In the ECT group, the troponin T values were also correlated with periprocedural heart rate and blood pressure values. Because of organizational or technical reasons, the measurement was not performed in all patients. RESULTS: Twenty patients undergoing ECT and 6 patients with epilepsy with a GCS during VEM were included. Postictal echocardiography showed no wall motion disorders and no change in left ventricular and right ventricular functions. Four of 17 patients displayed a transient increase in high-sensitive cardiac troponin T 4-6 h after the seizure (3 patients with ECT-induced seizure). None of these 4 patients had signs of an acute cardiac event, and periprocedural blood pressure or heart rate peaks during ECT did not significantly differ in patients with and without troponin T elevation. CONCLUSIONS: Signs of mild cardiac stress can occur in some patients following ECT or GCS without clinical complications, probably related to excessive catecholamine release during the seizure.

Neurogenic pulmonary edema following seizures: A retrospective computed tomography study.

INTRODUCTION: Data on the frequency and clinical relevance of neurogenic pulmonary edema (NPE) following epileptic seizures are limited. The aim of the present study was to analyze computed tomography (CT) examinations in patients with previous seizures. METHOD: Incidence of NPE and related clinical factors were retrospectively assessed in patients admitted because of epileptic seizures who underwent thoracic CT imaging as part of emergency diagnostics. RESULTS: Between January 2010 and January 2016, we included all patients admitted with the International Classification of Diseases (ICD) diagnosis code of epileptic seizure or epilepsy and who underwent CT imaging, including visualization of the lungs, as part of emergency diagnostics. Of the 47 included patients, 26 patients had suffered from generalized convulsive seizures (GCS), 17 patients had focal seizures with impaired and 4 without impaired consciousness. Signs of NPE were present in 5 out of 47 patients; all 5 patients had GCS prior to thoracic CT scan (i.e., 19% of patients with GCS). In four out of five cases, a single seizure was described; in one case, the seizure was only partially witnessed, but the indirect clinical signs strongly suggested a GCS. Related factors such as the initial respiratory rate or the initial pCO2 value were not significantly different in patients with and without signs of NPE. CONCLUSIONS: The highly selected and biased patient group warrants caution in the interpretation of the study results. Our data, however, confirm that signs of NPE appear to be rather frequent in patients with GCS. Its clinical significance as regards morbidity and sudden death in epilepsy is discussed.

The discriminative value of blood gas analysis parameters in the differential diagnosis of transient disorders of consciousness.

AIM: The differentiation between epileptic and non-epileptic episodes can be challenging. Our aim was to compare lactate, anion gap (AG), bicarbonate and the Denver Seizure Score (DSS) as point-of-care test (POCT) markers for episodes of transient alterations of consciousness. METHODS: The blood serum parameters were drawn at arrival in the emergency department (ED) within 2 h of the episode. After calculating AG and DSS values, the four parameters were compared retrospectively between patients with generalized tonic-clonic seizures (GTCS) (n = 165) and patients with other disorders of consciousness [syncopes (n = 43), and psychogenic non-epileptic seizures (n = 15)]. Additionally, we compared all values among men and women. RESULTS: In GTCS patients, all four parameters differed significantly compared to non-epileptic episode patients (p < 0.001). Serum lactate showed significant additional benefit over the remaining values, with an AUC of 0.947 (95% CI 0.92-0.975) and a high sensitivity and specificity for an optimal cut-off value of 2.45 mmol/l. For DSS, the AUC was 0.857 (95% CI 0.808-0.906; cut-off: 0.35), and for AG 0.836 (95% CI 0.783-0.889; cut-off: 12.45 mmol/l). In the case of serum bicarbonate, the AUC was 0.831 (95% CI 0.775-0.886; cut-off: 22.75 mmol/l). In the sex-dependent comparison, the results were similar. Men showed more significant differences in the compared values than women. CONCLUSIONS: Serum lactate is best suited as POCT marker in the differential diagnosis of epileptic and non-epileptic episodes and is superior to AG, DSS and bicarbonate. The differences among sexes may pose a challenge in their implementation and interpretation.