Discontinuation of Antiseizure Medications in Patients With Brain Tumors.

Patients with brain tumors will experience seizures during their disease course. While providers can use antiseizure medications to control these events, patients with brain tumors can experience side effects, ranging from mild to severe, from these medications. Providers in subspecialties such as neurology, neuro-oncology, neurosurgery, radiation oncology, and medical oncology often work with patients with brain tumor to balance seizure control and the adverse toxicity of antiseizure medications. In this study, we sought to explore the problem of brain tumor-related seizures/epilepsy in the context of how and when to consider antiseizure medication discontinuation. Moreover, we thoroughly evaluate the literature on antiseizure medication discontinuation for adult and pediatric patients and highlight recommendations relevant to patients with both brain tumors and seizures.

Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial.

Importance: Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically. Objective: To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma. Design, Setting, and Participants: Randomized clinical trial of 100 patients with a newly diagnosed (<6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. Participants were enrolled at the Norwegian National Unit for Vestibular Schwannoma from October 28, 2014, through October 3, 2017; 4-year follow-up ended on October 20, 2021. Interventions: Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires. Main Outcomes and Measures: The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications. Results: Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P = .002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed. Conclusion and relevance: Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02249572.

Seizure Management and Prophylaxis Considerations in Patients with Brain Tumors.

PURPOSE OF REVIEW: The article gives an overview of the current knowledge in the management of tumor related epilepsy, including systematic reviews and consensus statements as well as recent insight into a potentially more individualized treatment approach. RECENT FINDINGS: Tumor molecular markers as IDH1 mutation and MGMT methylation status may provide future treatment targets. Seizure control should be included as a metric in assessing efficacy of tumor treatment. Prophylactic treatment is recommended in all brain tumor patients after the first seizure. Epilepsy has a profound effect on the quality of life in this patient group. The clinician should tailor the choice of seizure prophylactic treatment to the individual patient, with the goal of limiting adverse effects, avoiding interactions and obtaining a high degree of seizure freedom. Status epilepticus is associated with inferior survival and must be treated promptly. A multidisciplinary team should treat patients with brain tumors and epilepsy.

[Brain metastases ­ diagnostics and treatment] / Hjernemetastasar ­ diagnostikk og behandling.

An ageing population as well as improved diagnostics, monitoring and treatment mean that an increasing incidence of brain metastases can be expected. Patients with brain metastases were previously regarded as a homogenous group with a very poor prognosis. However, the current picture is more complex. The development of new treatment methods, better molecular understanding and personalised medicine require a focus on multidisciplinary collaboration to provide optimal treatment for individual patients. This clinical review article provides an overview of important factors related to the diagnosis and treatment of patients with brain metastases.

Limbic Encephalitis following Allogeneic Hematopoietic Stem Cell Transplantation.

A woman with myelodysplastic syndrome (MDS) was treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). 65 days after the transplantation, she developed fatigue and central neurological symptoms. Clinical workup including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination revealed findings suspicious for limbic encephalitis (LE), successfully treated with intravenous immunoglobulins and intravenous corticosteroids. Although a rare complication after allo-HSCT, physicians should be aware of neurological symptoms that develop throughout the transplantation course.

Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Antiseizure medication in patients with Glioblastoma- a collaborative cohort study.

PURPOSE: We investigated, whether epileptic seizures (ES) as presenting symptom in adult patients with GBM are associated with better Overall Survival (OS) compared to ES presenting later during the course of GBM, and efficacy and safety of different antiseizure medications (ASMs). METHODS: Retrospective consecutive cohort study of adults with GBM: 50 from Norway and 50 from Italy. We compared the time to changing ASM treatments. OS was investigated with a Cox regression model adjusted for time dependency. RESULTS: Median follow-up was 17 months from GBM diagnosis. ES were the presenting symptom in 49 patients. All patients received ASM treatment. LEV was the first ASM in the majority of patients and the most effective at one year from the first prescription, (p = 0.004). Occurrence of adverse events (AEs) was similar between LEV and other ASMs (p = 0.47). Poorer OS correlated with older age at GBM diagnosis, country and ASM therapy. A negative impact of ASMs on OS was observed for LEV in a univariate and multivariate analysis, and for VPA (only in multivariate analysis), even when adjusted for O6-methylguanine-DNA-methyltransferase (MGMT) methylation status. Patients with ES as the onset symptom of GBM and patients who had first ES later had similar OS (p = 0.87). CONCLUSION: ES as the GBM debut symptom did not lead to a longer OS. LEV was a more effective ASM compared to other treatments with no differences regarding AEs between LEV and other ASMs. Surprisingly, in our patients LEV and VPA were associated with worse OS than other ASMs. This result should be interpreted with caution due to the retrospective nature of this study along with the many variables which may affect the outcome in this population.

Comparing the impact of upfront radiosurgery versus expectation in vestibular schwannoma (the V-REX study): protocol for a randomised, observer-blinded, 4-year, parallel-group, single-centre, superiority study.

INTRODUCTION: The optimal management of small-sized to medium-sized vestibular schwannoma (VS) is a matter of controversy. Clinical results of the prevailing treatment modalities (microsurgery, stereotactic radiosurgery (SRS), and conservative management (CM)) are documented, but comparative studies are few, and none are randomised or blinded. Upfront radiosurgery, or a careful follow-up by MRI with subsequent treatment on growth, are two strategies used at many centres. The present study aims at comparing these strategies by randomising individuals with newly diagnosed tumours to either upfront SRS or initial CM. METHODS AND ANALYSIS: The Vestibular Schwannoma: Radiosurgery or Expectation study is designed as a randomised, controlled, observer-blinded, single-centre superiority trial with two parallel groups. Eligible patients will be randomised using sequentially numbered opaque sealed envelopes, and the radiosurgery group will undergo standard Gamma Knife Radiosurgery (GKRS) within 2 months following randomisation. The primary endpoint is tumour growth measured as volume ratio V4years/Vbaseline and volume doubling time, evaluated by annual T1 contrast MRI volumetric analysis. Secondary endpoints include symptom and sign development measured by clinical examination, audiovestibular tests, and by patient's responses to standardised validated questionnaires. In addition, the patient's working status, and the health economics involved with both strategies will be evaluated and compared. All outcome assessments will be performed by blinded observers. Power analysis indicates that 100 patients is sufficient to demonstrate the effect of GKRS on tumour volume. ETHICS AND DISSEMINATION: The trial has ethical approval from the Regional Ethical Committee (23503) and funding from The Western Norway Regional Health Authority. Trial methods and results will be reported according to the Consolidated Standards of Reporting Trials 2010 guidelines in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Clinical trials: NCT02249572. Haukeland University Hospital record: 2014/314. Regional Ethical Committee (REC West): 23 503. The Western Norway Regional Health Authority: 912 281.

Experiences, distress and burden among neurologists in Norway during the COVID-19 pandemic.

BACKGROUND: The ongoing COVID-19 pandemic has caused rapid changes in the healthcare system. Workforce reorganization, reduced standard of care and a lack of personal protection equipment (PPE) for health care workers were among the concerns raised in the first wave of the pandemic. Our aim was to explore the experiences, distress and burden among Norwegian neurologists during the first weeks of the pandemic. METHODS: Hospital-based neurologists in Norway (n = 400) were invited to a web-based survey in April 2020. The study focused on patient management, organizational changes and personal stress during the first weeks of the pandemic lockdown. Work-home interface stress was assessed by the Cooper Job Stress Questionnaire. RESULTS: In total, 135 neurologists participated. Seventy-three% experienced a change in their personal work situation, and 67% examined patients with suspected COVID-19 infection and neurological disease. Changed access to resources, and the perception that medical follow-up was unsatisfactory, were associated with a high degree of burden and stress. Neurologists were also worried about the potential lack of PPE and the fear of spreading SARS CoV-2 to close family members. The mean score of work-home interface stress was 2.8 with no significant differences between gender or specialist status. Reduced standard of care was reported for all neurological conditions, and in particular for non-emergency treatments. CONCLUSION: The vast majority of neurologists in Norway experienced a change in their personal work situation during the first phase of the pandemic. The fear of becoming infected and ill was not a major contributor to burden and stress.

Acute stroke care during the first phase of COVID-19 pandemic in Norway.

OBJECTIVES: The aim of the present study was to investigate how the initial phase of the COVID-19 pandemic affected the hospital stroke management and research in Norway. MATERIALS AND METHODS: All neurological departments with a Stroke Unit in Norway (n = 17) were invited to participate in a questionnaire survey. The study focused on the first lockdown period, and all questions were thus answered in regard to the period between 12 March and 15 April 2020. RESULTS: The responder rate was 94% (16/17). Eighty-one % (13/16) reported that the pandemic affected their department, and 63% (10/16) changed their stroke care pathways. The number of new acute admissions in terms of both strokes and stroke mimics decreased at all 16 departments. Fewer patients received thrombolysis and endovascular treatment, and multidisciplinary stroke rehabilitation services were less available. The mandatory 3 months of follow-up of stroke patients was postponed at 73% of the hospitals. All departments conducting stroke research reported a stop in ongoing projects. CONCLUSION: In Norway, hospital-based stroke care and research were impacted during the initial phase of the COVID-19 pandemic, with likely repercussions for patient care and outcomes. In the future, stroke departments will require contingency plans in order to protect the entire stroke treatment chain.

Experiences of telemedicine in neurological out-patient clinics during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has led to rapid changes in the delivery of medical care worldwide. The main objective of this survey was to investigate the initial experiences of neurologists with the use of telemedicine for different neurological conditions during the first phase of the COVID-19. METHODS: All hospital-based neurologists in Norway (n = 400) were invited to a questionnaire survey by e-mail in April 2020. The study focused on telemedicine and all questions were answered with regard to the first weeks of the pandemic lockdown in Norway. RESULTS: One-hundred and thirty-five neurologists responded. Overall, 87% reported a shift toward more telemedicine, with significantly more use of telephone than video consultations for both new referrals (54% vs. 30%, P < 0.001) and follow-ups (99% vs. 50%, P < 0.001). Respondents deemed it much more professionally satisfactory to conduct follow-up consultations by telephone, than to carry out consultations with new patients by telephone (85% vs. 13%, P < 0.001). Teleconsultations were better suited for headache and epilepsy patients as compared to multiple sclerosis and movement disorder patients. There was no significant difference between residents and senior consultants regarding how they experienced teleconsultations. Female neurologists found telemedicine better and more effective than male neurologists. INTERPRETATION: Telemedicine was rapidly implemented in Norwegian neurological departments during the first weeks of the COVID-19 pandemic. Teleconsultations were better suited for follow-ups than for new referrals, and better for headache and epilepsy patients as compared to multiple sclerosis and movement disorder patients.

Correction to: Hospital-based headache care during the Covid-19 pandemic in Denmark and Norway.

An amendment to this paper has been published and can be accessed via the original article.

Hospital-based headache care during the Covid-19 pandemic in Denmark and Norway.

BACKGROUND: The Covid-19 pandemic is causing changes in delivery of medical care worldwide. It is not known how the management of headache patients was affected by the lockdown during the pandemic. The aim of the present study was to investigate how the initial phase of the Covid-19 pandemic affected the hospital management of headache in Denmark and Norway. METHODS: All neurological departments in Denmark (n = 14) and Norway (n = 18) were invited to a questionnaire survey. The study focused on the lockdown and all questions were answered in regard to the period between March 12th and April 15th, 2020. RESULTS: The responder rate was 91% (29/32). Of the neurological departments 86% changed their headache practice during the lockdown. The most common change was a shift to more telephone consultations (86%). Video consultations were offered by 45%. The number of new headache referrals decreased. Only 36% administered botulinum toxin A treatment according to usual schemes. Sixty% reported that fewer patients were admitted for in-hospital emergency diagnostics and treatment. Among departments conducting headache research 57% had to halt ongoing projects. Overall, 54% reported that the standard of care was worse for headache patients during the pandemic. CONCLUSION: Hospital-based headache care and research was impacted in Denmark and Norway during the initial phase of the Covid-19-pandemic.

Antiepileptic and psychiatric medication in a nationwide cohort of patients with glioma WHO grade II-IV.

INTRODUCTION: Glioma is the most common intracranial primary brain tumor. Patients with glioma often suffer from epilepsy, anxiety and depression. Aims of this study were to identify risk factors for drug-treated anxiety and depression, and to determine the use of psychiatric medication in a national glioma cohort. METHODS: Data from the Cancer Registry of Norway on all persons diagnosed with glioma WHO grade II-IV 2004-2010 were linked with data from the Norwegian Prescription Database. Cox regression analysis was used to assess risk factors for drug-treated anxiety and depression. Standardized incidence ratios were calculated for psychiatric medication dispensed to glioma patients and compared to the general population. RESULTS: The glioma cohort consisted of 1056 males and 772 females. Of the 1828 patients, 565 had glioma grade II-III, and 1263 had grade IV. The patients with glioma grade II-III who were treated with levetiracetam had an increased risk for drug-treated anxiety compared to patients without levetiracetam; hazard ratio 2.8 (95% confidence interval 1.7-4.9). Female gender increased the risk for drug-treated anxiety compared to males in patients with glioma grade IV; hazard ratio 1.5 (95% confidence interval 1.2-2.0). Antidepressants were less frequently dispensed to patients with glioma grade II-III and epilepsy than to the general population. CONCLUSIONS: Patients with glioma grade II-III on levetiracetam had an increased risk for drug-treated anxiety. The subgroup of patients with glioma grade II-III and epilepsy received less antidepressants than the general population.

Cerebellar degeneration-related proteins 2 and 2-like are present in ovarian cancer in patients with and without Yo antibodies.

BACKGROUND: Cerebellar degeneration-related protein 2 (CDR2) has been presumed to be the main antigen for the onconeural antibody Yo, which is strongly associated with ovarian cancer and paraneoplastic cerebellar degeneration (PCD). Recent data show that Yo antibodies also target the CDR2-like protein (CDR2L). We, therefore, examined the expression of CDR2 and CDR2L in ovarian cancer tissue from patients with and without Yo antibodies and from various other cancerous and normal human tissues. METHODS: Ovarian cancer tissue and serum samples from 16 patients were included in the study (four with anti-Yo and PCD, two with anti-Yo without PCD, five with only CDR2L antibodies, and five without onconeural antibodies). Clinical data were available for all patients. The human tissues were examined by western blot and immunohistochemistry using rabbit CDR2 and CDR2L antibodies. RESULTS: Ovarian cancers from all 16 patients expressed CDR2 and CDR2L proteins. Both proteins were also present in normal and cancer tissue from mammary tissue, kidney, ovary, prostate, and testis. CONCLUSION: CDR2L is present in ovarian cancers from patients with and without Yo antibodies as was shown previously for CDR2. In addition, both CDR2 and CDR2L proteins are more widely expressed than previously thought, both in normal and cancerous tissues.

Epidemiology of Parkinson's disease.

Parkinson's disease (PD) affects 1-2 per 1000 of the population at any time. PD prevalence is increasing with age and PD affects 1% of the population above 60 years. The main neuropathological finding is α-synuclein-containing Lewy bodies and loss of dopaminergic neurons in the substantia nigra, manifesting as reduced facilitation of voluntary movements. With progression of PD, Lewy body pathology spreads to neocortical and cortical regions. PD is regarded as a movement disorder with three cardinal signs: tremor, rigidity and bradykinesia. A recent revision of the diagnostic criteria excludes postural instability as a fourth hallmark and defines supportive criteria, absolute exclusion criteria and red flags. Non-motor symptoms in PD have gained increasing attention and both motor and non-motor signs are now included among the supportive criteria. The cause of PD is unknown in most cases. Genetic risk factors have been identified, including monogenetic causes that are rare in unselected populations. Some genetic factor can be identified in 5-10% of the patients. Several environmental factors are associated with increased risk of PD. Autopsy studies show that the clinical diagnosis of PD is not confirmed at autopsy in a significant proportion of patients. Revised diagnostic criteria are expected to improve the clinician´s accuracy in diagnosing PD. Increasing knowledge on genetic and environmental risk factors of PD will probably elucidate the cause of this disease within the near future.

Status epilepticus secondary to glioma.

PURPOSE: Epilepsy is common in glioma patients, but clinical data on the course of status epilepticus (SE) in this group are sparse. The aim of this study was to investigate the relationship of SE to tumor grading, seizure semiology, trigger factors, treatment response, recurrence and outcome of SE in patients with glioma. METHODS: Adult patients with SE and glioma WHO grade II-IV were identified from a prospective clinical study at two neurological departments. We identified 31 SE in 20 patients during a period of 7 years. RESULTS: SE was more frequent in patients with high-grade glioma. Half of the seizures were secondary generalized. Patients with a clinical and radiological stable glioma had SE as often as patients with untreated tumor or tumor in progression. The majority of patients had a well-controlled epilepsy prior to SE. SE responded well to first and second line treatment. Patients with SE and tumor progression were not more refractory to treatment than patients without progression. CONCLUSION: SE secondary to glioma responded well to treatment and should be treated aggressively regardless of the oncological prognosis. Seizures during tumor progression were not more treatment refractory than SE in patients with stable glioma disease.

Does the choice of antiepileptic drug affect survival in glioblastoma patients?

Patients with glioblastoma (GBM) often suffer from symptomatic epilepsy. Older antiepileptic drugs (AEDs) which affect the enzyme system cytochrome P450 have been in extensive use, but there is an increasing focus on interactions with other drugs. This study investigated whether newer AEDs with little or no enzyme effect are increasingly preferred. Previous research has indicated that valproate improves survival in GBM. We investigated the impact of AEDs on overall survival in GBM patients. All GBM patients diagnosed in Norway 2004-2010 were included through a linkage of national registries, and follow-up data on the malignancy and drug usage were analyzed. In a multivariate cox proportional-hazards regression, AEDs were adjusted for each other and for relevant factors. Immortal time bias was eliminated with time-dependent variables. The study population was 1263 patients with histologically confirmed GBM. Carbamazepine was the most frequently prescribed AED to patients diagnosed with GBM during 2004-2006, while levetiracetam was increasingly prescribed to patients diagnosed later. Taking AEDs on a reimbursement code of epilepsy was not beneficial for survival. None of the six AEDs valproate, levetiracetam, carbamazepine, oxcarbazepine, lamotrigine or phenytoin significantly altered overall survival. There has been a shift in the prescriptions of AEDs to GBM patients from older to newer AEDs over time. We found no significant survival benefit in GBM patients neither from treatment with AEDs for epilepsy in general, nor from the usage of six separate AEDs.