The First Neuropalliative Care Unit in Germany-Characteristics of Patients.

A unique structure of care for neurological inpatients with significant palliative care (PC) needs was established in the Department of Neurology at the Charité-Universitätsmedizin Berlin in 2021: a specialized neuropalliative care (NPC) unit. After one year, we provide an overview of the concept and the patients' characteristics. METHODS: We retrospectively analyzed the characteristics of patients treated in our NPC unit between February 2021-February 2022. Data were extracted from medical records and PC assessment including diagnosis, mode of admission and discharge, length of stay, and palliative symptoms. Data are presented as averages with a 95% confidence interval [lower limit; upper limit] or percentage (absolute number). RESULTS: We included 143 patients (52% (75) female, 67.9 years [65.6; 70.2]). Patients were admitted from general wards (48%; 68), their homes (22%; 32), intensive care units (16%; 23) or emergency departments (14%; 20). The main diagnoses were tumors of the nervous system (39%; 56), neurodegenerative diseases (30%; 43), neurologic complications (13%; 19) and cerebrovascular diseases (12%; 17). Complaints most frequently rated as severely to overwhelmingly burdensome were motor- or fatigue-associated problems, problems communicating, dysphagia and pain. The average length of stay was 13.7 days [12.2; 15.2]. Forty-five percent (64) of patients were discharged without further PC, 17% (24) were referred to a hospice and 13% (18) were discharged with outpatient PC. Five percent (7) were referred to neurorehabilitation and 21% (30) of patients died. CONCLUSIONS: Our NPC unit is a new model of care for neurological patients with substantial PC needs especially within the structures of a highly specialized and individualized medicine.

Causes for Emergency Hospitalization of Neurological Patients With Palliative Care Needs.

Background: Acute and unexpected hospitalization can cause serious distress, particularly in patients with palliative care needs. Nevertheless, the majority of neurological inpatients receiving palliative care are admitted via an emergency department. Objective: Identification of potentially avoidable causes leading to acute hospitalization of patients with neurological disorders or neurological symptoms requiring palliative care. Methods: Retrospective analysis of medical records of all patients who were admitted via the emergency department and received palliative care in a neurological ward later on (n = 130). Results: The main reasons for acute admission were epileptic seizures (22%), gait disorders (22%), disturbance of consciousness (20%), pain (17%), nutritional problems (17%), or paresis (14%). Possible therapy limitations, (non)existence of a patient decree, or healthcare proxy was documented in only 31%. Primary diagnoses were neoplastic (49%), neurodegenerative (30%), or cerebrovascular (18%) diseases. Fifty-nine percent were directly admitted to a neurological ward; 25% needed intensive care. On average, it took 24 h until the palliative care team was involved. In contrast to initially documented problems, key challenges identified by palliative care assessment were psychosocial problems. For 40% of all cases, a specialized palliative care could be organized. Conclusion: Admissions were mainly triggered by acute events. Documentation of the palliative situation and treatment limitations may help to prevent unnecessary hospitalization. Although patients present with a complex symptom burden, emergency department assessment is not able to fully address multidimensionality, especially concerning psychosocial problems. Prospective investigations should develop short screening tools to identify palliative care needs of neurological patients already in the emergency department.

Etiology-specific response to antiseizure medication in focal epilepsy.

OBJECTIVE: In focal epilepsy, data on the etiology-specific response to antiseizure medication (ASM) are surprisingly sparse. In this study, we sought to reappraise whether seizure outcome of pharmacological treatment is linked to the underlying etiology. Furthermore, we assessed ASM load with respect to the cause of epilepsy. METHODS: Data were retrospectively obtained from the electronic database of the three sites of an academic adult epilepsy outpatient clinic. For each patient, presumed cause of epilepsy was categorized into one of nine etiological groups. Individual drug loads were calculated according to the 2020 World Health Organization Center for Drug Statistics Methodology ATC/DDD Index. Univariate and multivariate analyses were conducted to explore the association between different etiologies and outcome regarding 12-month seizure freedom as well as ASM load. RESULTS: A total of 591 patients with focal epilepsy were included in the final analysis. Ischemic stroke was the etiology with the highest rate of 12-month terminal seizure freedom (71.2%, 95% confidence interval [CI] = 57.9-82.2) and, considering all etiological groups, was an independent predictor of seizure freedom (odds ratio = 2.093, 95% CI = 1.039-4.216). The lowest rates of seizure freedom were observed in patients with hippocampal sclerosis (28.2%, 95% CI = 15.0-44.9) and malformation of cortical development (16.7%, 95% CI = 2.1-48.4). In patients with ischemic stroke, median ASM load (1.0, interquartile range [IQR] = .5-1.8) was significantly lower compared to that in patients with hippocampal sclerosis (median = 1.8, IQR = 1.2-3.0, p = .008) and brain tumors (median = 1.7, IQR = .7-3.2, p = .049). SIGNIFICANCE: Response to treatment with ASM is highly etiology-specific and best in patients with epilepsy due to ischemic stroke. Interestingly, this most favorable treatment outcome can be achieved by the lowest ASM load considering all etiological groups. In focal epilepsy, etiology should be taken into account when counseling patients about their expected seizure outcome with pharmacological treatment and when tailoring initial ASM doses.

Surgery in intractable epilepsy-physicians' recommendations and patients' decisions.

OBJECTIVES: To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video-EEG monitoring (sca-VEM), semi-invasive (sem-)VEM with foramen ovale and/or peg electrodes, and invasive (in-)VEM. METHODS: Consecutive patients, who underwent presurgical assessment with at least one sca-VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. RESULTS: Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca-, 36 sem-, and 57 in-VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca- or additional sem-VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in-VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in-VEM comprised intellectual disability (OR 4.721, 95% CI 1.047-21.284), extratemporal focal aware non-motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124-0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100-0.614 and 0.149, 95% CI 0.027-0.829, respectively). CONCLUSIONS: During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations.

Human Cerebrospinal Fluid Monoclonal LGI1 Autoantibodies Increase Neuronal Excitability.

OBJECTIVE: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common antibody-mediated encephalopathy, but insight into the intrathecal B-cell autoimmune response, including clonal relationships, isotype distribution, frequency, and pathogenic effects of single LGI1 antibodies, has remained limited. METHODS: We cloned, expressed, and tested antibodies from 90 antibody-secreting cells (ASCs) and B cells from the cerebrospinal fluid (CSF) of several patients with LGI1 encephalitis. RESULTS: Eighty-four percent of the ASCs and 21% of the memory B cells encoded LGI1-reactive antibodies, whereas reactivities to other brain epitopes were rare. All LGI1 antibodies were of IgG1, IgG2, or IgG4 isotype and had undergone affinity maturation. Seven of the overall 26 LGI1 antibodies efficiently blocked the interaction of LGI1 with its receptor ADAM22 in vitro, and their mean LGI1 signal on mouse brain sections was weak compared to the remaining, non-ADAM22-competing antibodies. Nevertheless, both types of LGI1 antibodies increased the intrinsic cellular excitability and glutamatergic synaptic transmission of hippocampal CA3 neurons in slice cultures. INTERPRETATION: Our data show that the patients' intrathecal B-cell autoimmune response is dominated by LGI1 antibodies and that LGI1 antibodies alone are sufficient to promote neuronal excitability, a basis of seizure generation. Fundamental differences in target specificity and antibody hypermutations compared to the CSF autoantibody repertoire in N-methyl-D-aspartate receptor encephalitis underline the clinical concept that autoimmune encephalitides are very distinct entities. Ann Neurol 2020;87:405-418.

Referral to evaluation for epilepsy surgery: Reluctance by epileptologists and patients.

OBJECTIVE: Despite the obvious advantages of resective surgery in patients with drug-resistant focal epilepsy, namely high probability of seizure freedom, decreased mortality, and increased quality of life, referral rates from physicians and approval rates by patients for presurgical assessment remain constantly low. METHODS: In the outpatient clinics of a tertiary epilepsy center, checklists were implemented asking treating epileptologists whether they recommended presurgical evaluation with noninvasive video-electroencephalographic monitoring to adult patients with drug-resistant focal epilepsy and asking respective patients whether they followed this recommendation. RESULTS: Of 185 eligible patients, 80 (43%) were recommended presurgical evaluation by their epileptologists, and 24 (30%) of these patients consented. Nineteen of all patients (10%) actually underwent noninvasive presurgical assessment, and nine of these eventually proceeded to resection. The most frequent reason for nonreferral by epileptologists was their subjective appraisal of seizure frequency as low (31%), whereas patients declined most often due to overall fear of brain surgery (50%). Variables independently associated with nonreferral by epileptologists comprised older age of patients at questioning (odds ratio [OR] = 1.03), no previous evaluation for epilepsy surgery (OR = 4.04), the presence of legal guardianship (OR = 4.29), and ≥11 years of professional experience by the treating epileptologist (OR = 4.62). Independent predictors for patients' rejection of presurgical evaluation were older age at questioning (OR = 1.08), lifetime number of antiepileptic drugs ≥ 5 (OR = 4.47), presence of focal aware seizures (OR = 4.37), and absence of focal seizures with impaired awareness (OR = 11.24). SIGNIFICANCE: In both epileptologists and patients with difficult-to-treat epilepsy, we found high decision rates against presurgical assessment. Some reasons given by physicians for not recommending presurgical evaluation to patients may be understandable; others need further exploration. On the patients' side, early and thorough counseling on risks and benefits of epilepsy surgery is necessary to increase understanding and acceptance.