Glioblastoma in the oldest old: Clinical characteristics, therapy, and outcome in patients aged 80 years and older.

Background: Incidence rates of glioblastoma in very old patients are rising. The standard of care for this cohort is only partially defined and survival remains poor. The aims of this study were to reveal current practice of tumor-specific therapy and supportive care, and to identify predictors for survival in this cohort. Methods: Patients aged 80 years or older at the time of glioblastoma diagnosis were retrospectively identified in 6 clinical centers in Switzerland and France. Demographics, clinical parameters, and survival outcomes were annotated from patient charts. Cox proportional hazards modeling was performed to identify parameters associated with survival. Results: Of 107 patients, 45 were diagnosed by biopsy, 30 underwent subtotal resection, and 25 had gross total resection. In 7 patients, the extent of resection was not specified. Postoperatively, 34 patients did not receive further tumor-specific treatment. Twelve patients received radiotherapy with concomitant temozolomide, but only 2 patients had maintenance temozolomide therapy. Fourteen patients received temozolomide alone, 35 patients received radiotherapy alone, 1 patient received bevacizumab, and 1 took part in a clinical trial. Median progression-free survival (PFS) was 3.3 months and median overall survival (OS) was 4.2 months. Among patients who received any postoperative treatment, median PFS was 3.9 months and median OS was 7.2 months. Karnofsky performance status (KPS) ≥70%, gross total resection, and combination therapy were associated with better outcomes. The median time spent hospitalized was 30 days, accounting for 23% of the median OS. End-of-life care was mostly provided by nursing homes (n = 20; 32%) and palliative care wards (n = 16; 26%). Conclusions: In this cohort of very old patients diagnosed with glioblastoma, a large proportion was treated with best supportive care. Treatment beyond surgery and, in particular, combined modality treatment were associated with longer OS and may be considered for selected patients even at higher ages.

A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol.

BACKGROUND: Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma. METHODS/DESIGN: GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland. TRIAL REGISTRATION: NCT05664464. Registered 23 December 2022.

Laser Interstitial Thermal Therapy in a Large Thalamic Glioma with Long-Term Remission: A Case Report.

INTRODUCTION: Thalamic gliomas pose a particular therapeutic challenge as complete resection is rarely achieved due to the deep and eloquent location. Laser interstitial thermal therapy (LITT) may provide a valuable management option for deep-seated gliomas that are not accessible with open surgery. CASE PRESENTATION: A 57-year-old woman presented with a rapidly progressive large thalamic glioblastoma. Opting for full ablation, we selected a challenging trajectory to maximize the possibility of full ablation. At 2.4 cm in diameter, the tumour was larger than recommended for LITT; nevertheless, three laser ablations along a single trajectory resulted in macroscopic ablation without complications. Adjuvant radio-chemotherapy was started soon after surgery without radiological recurrence 1.5 years after the initial surgery. CONCLUSION: This case demonstrates the potential when thalamic tumours are managed with timely LITT treatment and meticulous trajectory planning. Moreover, it highlights the need for close interdisciplinary management with neurosurgeons, neuropathologists, neuroradiologists, and neurooncologists.

Neuropathies related to hepatitis E virus infection: A prospective, matched case-control study.

BACKGROUND: Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking. AIMS: To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population. METHODS: Swiss multicenter, prospective, observational, matched case-control study over 3 years (September 2019-October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti-HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real-time polymerase chain reaction (RT-PCR). RT-PCR was performed on sera to confirm IgM positivity. RESULTS: We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti-HEV IgM-positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = -0.25) was observed only between acute HEV infection and NA. CONCLUSION: This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy.

Immune checkpoint inhibitors induced side effects of the peripheral nervous system.

PURPOSE OF REVIEW: This review highlights recent knowledge on the diagnosis and treatment of immune checkpoint inhibitor-induced neurological side effects (irNAE) focussing on the neuromuscular system. RECENT FINDINGS: irNAEs mainly resemble sporadic neuromuscular autoimmune diseases and paraneoplastic neurological syndromes. However, neurological symptoms may be unspecific (muscle weakness, fatigue) in the oncological setting and carry the risk of misdiagnosis and delayed therapeutic intervention. The role of disease-specific neuromuscular autoantibodies in the diagnosis is controversial as preexisting autoantibodies may otherwise be present before immune checkpoint inhibitor (ICI) treatment without clinical symptoms and may not develop in case of irNAE manifestation. A new necrotising form of myositis (irMyositis) has been described presenting with facial weakness and ptosis mimicking myasthenia gravis. It comes along with a high rate of severe myocarditis accounting for a triad overlap syndrome (myasthenia/myositis/myocarditis). The role of modern biologicals in the treatment of irNAEs has to be determined. SUMMARY: irNAEs are rare but carry the risk of permanent morbidity and mortality. Early suspicion and diagnosis are key to prevent neurological sequelae. Beyond interruption of ICI administration, treatment corresponds to sporadic autoimmune diseases. The myasthenia/myositis/myocarditis overlap syndrome deserves special attention as it carries the highest risk of mortality. The role of neurotoxic pretreatment regimens, preexisting subclinical neurological autoimmune diseases and the risk of ICI-re-challenge after irNAEs has to be further investigated.

Correlation between age and the sciatic nerve diameter in the first 2 years of life: A high-resolution ultrasound study.

AIM: To investigate the maturation of the peripheral nervous system by analyzing the cross-sectional area of the sciatic nerve during the first 2 years of life. METHODS: The sciatic nerve was examined by high-resolution ultrasound imaging in 52 children aged 0 days to 10 years, 45 of whom were younger than 2 years. The correlation between the cross-sectional area of the nerve and the age was statistically tested. A logarithmic regression analysis was performed to develop a logarithmic growth model of the cross-sectional area. RESULTS: There is a highly significant correlation between the age and the cross-sectional area of the sciatic nerve. The growth rate can well be described by a logarithmic model. INTERPRETATION: Based on the literature on the maturation of the median nerve and nerve roots and the findings of the present study, we conclude that both the proximal and the distal parts of the nerves of the peripheral nervous system increase simultaneously. WHAT THIS PAPER ADDS: Normative values for the size of the sciatic nerve in children.

Laser Interstitial Thermal Therapy for Radionecrosis.

Radiotherapy is widely used for brain tumors but can cause radiation necrosis (RN). Laser interstitial thermal therapy (LITT) is a relatively new therapeutic modality for RN and its impact on patient outcome is still not well understood. Based on a systematic literature search (n=33), the authors discuss the available evidence. Most studies found a positive safety/efficacy profile, as LITT may help to lengthen survival, prevent progression, taper steroids, and improve neurological symptoms while remaining safe. Prospective studies on this subject are needed and may result in LITT becoming an essential therapeutic option for the treatment of RN.

Cerebrospinal Fluid HIV-1 Escape in Patients With Neurocognitive Symptoms: Pooled Data From a Neuro-HIV Platform and the NAMACO Study.

BACKGROUND: Despite modern antiretroviral therapy, human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) escape into the cerebrospinal fluid (CSF) may occur. We examined the prevalence of and factors associated with CSF HIV-1 escape among people living with HIV (PLWH) in Switzerland. SETTING: The Neurocognitive Assessment in the Metabolic and Aging Cohort study is an ongoing, prospective, longitudinal, multicenter study within the Swiss HIV Cohort Study. The neuro-HIV platform is a multidisciplinary, single-day outpatient consultation at Lausanne University Hospital. METHODS: We pooled data from the Neurocognitive Assessment in the Metabolic and Aging Cohort study and the neuro-HIV platform participants who underwent lumbar puncture between 2011 and 2019. Both patient groups had neurocognitive symptoms. Cerebrospinal fluid HIV-1 escape was defined as the presence of quantifiable CSF HIV-1 RNA when plasma HIV-1 RNA was suppressed or CSF HIV-1 RNA greater than plasma HIV-1 RNA when the latter was detectable. RESULTS: Of 1166 PLWH assessed, 288 underwent lumbar puncture. Cerebrospinal fluid HIV-1 escape was observed in 25 PLWH (8.7%) of whom 19 (76%) had suppressed plasma HIV-1 RNA. Characteristics of PLWH were comparable whether they had CSF HIV-1 escape or not, including comorbidities, time since HIV diagnosis (15 vs 16 years, P = 0.9), median CD4 nadir (158.5/mm 3 vs 171/mm 3 , P = 0.6), antiretroviral CSF penetration-effectiveness score (7 vs 7 points, P = 0.8), and neurocognitive diagnosis based on Frascati criteria and radiological findings. CONCLUSIONS: In this large pooled sample of PLWH with neurocognitive symptoms, CSF HIV-1 escape occurred in 8.7% of PLWH. People living with HIV with CSF HIV-1 escape presented no distinctive clinical or paraclinical characteristics. We conclude that lumbar puncture is unavoidable in confirming CSF HIV-1 escape.

Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study.

PURPOSE: Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862), a microtubule-destabilizing agent. The goal of this study (NCT02895360) was to characterize the safety, tolerability and antitumor activity of lisavanbulin administered as a 48-hour intravenous (IV) infusion at the recommended Phase 2 dose (RP2D) of 70 mg/m2. Results from the Phase 1 dose-escalation portion of the study identifying the RP2D have been previously reported. Here, we present the findings from the Phase 2a portion of this study. Methods. This multi-center, open-label study included patients with ovarian, fallopian-tube, or primary peritoneal cancer that was either platinum-resistant or refractory (11 patients), or with first recurrence of glioblastoma (12 patients). Lisavanbulin was administered as a 48-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle. Results. Lisavanbulin was well tolerated in both patient cohorts. Thirteen patients (56.5%) developed 49 adverse events assessed as related to study treatment. The majority were mild or moderate; four were grade 3/4. Sixteen SAEs were reported in nine patients (39.1%), with none considered related to study treatment. No AEs led to permanent treatment discontinuation. Three patients in the ovarian cancer cohort had stable disease with lesion size reductions after two cycles of treatment; in the glioblastoma cohort, one patient showed partial response with a > 90% glioblastoma area reduction as best response, and one patient had stable disease after eight cycles of treatment. Conclusion. This study demonstrated a favorable safety and tolerability profile of 48-hour continuous IV infusion of lisavanbulin in patients with solid extracranial tumors or glioblastoma. Clinicaltrials.gov registration: NCT02895360.

Symptom Burden in Glioblastoma: A Prospective Pilot Study from Diagnosis to First Progression.

INTRODUCTION: The evaluation of symptom burden, performance status, and neurological function is still challenging in glioblastoma (GBM) patients. Patients may suffer from a wide spectrum of neurological symptoms like cognitive deficits, aphasia, or hemiparesis, which interfere to report to comprehensive questionnaires. However, an integrated and reliable neuro-oncological assessment is the key in the clinical management and in the evaluation of treatment benefits for GBM patients. METHODS: We implemented an easy-to-use clinical toolkit for the prospective assessment and follow-up evaluation of GBM patients using the Karnofsky performance status (KPS), the National Institute of Health Stroke Scale (NIH-SS), and simple scores for the evaluation of key symptoms like fatigue, depression, and headache. RESULTS: We prospectively followed 50 patients. The composite score (headache, depression, and fatigue), fatigue alone, the NIHSS, and the KPS were suitable biomarkers to evaluate symptom burden in GBM patients and indicate clinical disease progression. DISCUSSION/CONCLUSION: The proposed clinical toolkit seems feasible in routine clinical practice and reflects changes in symptom burden in different stages of the postsurgical course of GBM patients in this monocentric clinical pilot trial.

Dataset of a retrospective multicenter cohort study on characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis.

Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited. We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis - two alternative causes of encephalitis - to increase the awareness of ICI-iE and improve its diagnosis and management. To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients' medical records and compared between the groups. The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders - ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis - are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections.

Characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis: A retrospective multicentre cohort study.

AIM: Immune checkpoint inhibitor-induced encephalitis (ICI-iE) is a rare but life-threatening toxicity of immune checkpoint inhibitor treatment. We aim to identify the characteristics of ICI-iE and describe factors that discriminate it from herpes simplex virus (HSV)-1 encephalitis and anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis, as two alternative entities of encephalitis. METHODS: In this retrospective multicentre cohort study, we collected patients with ICI-iE reported to the Side Effect Registry Immuno-Oncology from January 2015 to September 2021 and compared their clinical features and outcome with 46 consecutive patients with HSV-1 or anti-LGI1 encephalitis who were treated at a German neurological referral centre. RESULTS: Thirty cases of ICI-iE, 25 cases of HSV-1 encephalitis and 21 cases of anti-LGI1 encephalitis were included. Clinical presentation of ICI-iE was highly variable and resembled that of HSV-1 encephalitis, while impairment of consciousness (66% vs. 5%, p = .007), confusion (83% vs. 43%; p = .02), disorientation (83% vs. 29%; p = .007) and aphasia (43% vs. 0%; p = .007) were more common in ICI-iE than in anti-LGI1 encephalitis. Antineuronal antibodies (17/18, 94%) and MRI (18/30, 60%) were mostly negative in ICI-iE, but cerebrospinal fluid (CSF) showed pleocytosis and/or elevated protein levels in almost all patients (28/29, 97%). Three patients (10%) died of ICI-iE. Early immunosuppressive treatment was associated with better outcome (r = 0.43). CONCLUSIONS: ICI-iE is a heterogeneous entity without specific clinical features. CSF analysis has the highest diagnostic value, as it reveals inflammatory changes in most patients and enables the exclusion of infection. Early treatment of ICI-iE is essential to prevent sequelae and death.

Correlation of age and the diameter of the cervical nerve roots C5 and C6 during the first 2 years of life analyzed by high-resolution ultrasound imaging.

AIM: To analyze the increase in diameter of the nerve roots C5 and C6 in early childhood. METHODS: The nerve roots of 56 children aged 0 days to 10 years (47 younger than 2 years) were examined by high-resolution ultrasound imaging. The correlation of diameter and age was statistically tested and a logarithmic regression analysis was performed to develop a logarithmic growth model. RESULTS: The increase in nerve root diameter is greatest during the first 2 years of life and then the growth rate decreases steadily. The relationship between age and diameter follows a logarithmic curve (p < 10-8 ). INTERPRETATION: The main increase in the diameter of the nerve roots happens in the first 2 years of life. Comparing data from a previous study, our data also suggest that the maturation of the proximal part of the median nerve is comparable to the maturation of its distal segments. This suggests a synchronous maturation of the axons and myelin sheath for the whole extent of the nerve, from the radix to its very distal part. WHAT THIS PAPER ADDS: Normative values for the size of the cervical nerve roots C5 and C6; an insight into the maturation of the proximal parts of the peripheral nervous system; and the correlation between age and cervical root diameter.

Postoperative radiotherapy for meningiomas - a decision-making analysis.

BACKGROUND: The management of meningiomas is challenging, and the role of postoperative radiotherapy is not standardized. METHODS: Radiation oncology experts in Swiss centres were asked to participate in this decision-making analysis on the use of postoperative radiotherapy (RT) for meningiomas. Experts from ten Swiss centres agreed to participate and provided their treatment algorithms. Their input was converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies in clinical routine. RESULTS: Several criteria used for decision-making in postoperative RT in meningiomas were identified: histological grading, resection status, recurrence, location of the tumour, zugzwang (therapeutic need to treat and/or severity of symptoms), size, and cell division rate. Postoperative RT is recommended by all experts for WHO grade III tumours as well as for incompletely resected WHO grade II tumours. While most centres do not recommend adjuvant irradiation for WHO grade I meningiomas, some offer this treatment in recurrent situations or routinely for symptomatic tumours in critical locations. The recommendations for postoperative RT for recurrent or incompletely resected WHO grade I and II meningiomas were surprisingly heterogeneous. CONCLUSIONS: Due to limited evidence on the utility of postoperative RT for meningiomas, treatment strategies vary considerably among clinical experts depending on the clinical setting, even in a small country like Switzerland. Clear majorities were identified for postoperative RT in WHO grade III meningiomas and against RT for hemispheric grade I meningiomas outside critical locations. The limited data and variations in clinical recommendations are in contrast with the high prevalence of meningiomas, especially in elderly individuals.

[Palliative Care in Neurology]. / Palliative Care in der Neurologie.

Palliative Care in Neurology Abstract. Neurology as a discipline clearly overlaps with palliative care. Nevertheless, an early integration of palliative care accompanying neurological treatment rarely takes place, and there are still misunderstandings with regard to the timing of the inclusion of palliative care and its role beyond pure end-of-life care and hospice care. A further expansion and use of synergies should become an integral part of both disciplines in the coming years, and training should focus on appropriate training, especially for our young medical colleagues.

Assessment of neurological function using the National Institute of Health Stroke Scale in patients with gliomas.

BACKGROUND: The evaluation of treatment response in patients with gliomas is performed using the Response Assessment in Neuro-Oncology (RANO) criteria. These criteria are based on cerebral magnetic resonance imaging (MRI), steroid use, and neurological function. However, a standardized tool for evaluating neurological function was lacking. We compared changes in the National Institute of Health Stroke Scale (NIHSS) to changes in the RANO categories to determine the relationship between clinical and neuroradiological findings. METHODS: We reviewed data on all adult patients with supratentorial gliomas WHO grade II-IV who were treated at the Cantonal Hospital St. Gallen from 2008 to 2015. The NIHSS was performed prospectively at baseline and at 3-month intervals simultaneously to MRI. Associations between changes in the NIHSS and RANO categories were assessed using the Stuart-Maxwell test. RESULTS: Our cohort consisted of 61 patients from which 471 observations were analyzed. The most common histological diagnosis was glioblastoma (49.2%). In total, 74% of RANO categories and 81% of the NIHSS scores remained stable on follow-up. Statistically, contemporaneous changes in the RANO category did not correlate with changes in the NIHSS (P < .0001). CONCLUSION: The application of the NIHSS is easy and feasible in the heterogeneous population of glioma patients. In our cohort, the RANO categories did not reflect contemporaneous changes in the NIHSS. A validated clinical outcome measure with a well-defined minimal clinically important difference is warranted in neuro-oncological research and clinical practice.

Neurocognitive course at 2-year follow-up in a Swiss cohort of people with well-treated HIV.

OBJECTIVE: The aim of this study was to examine neurocognitive course over time among people with well treated HIV. DESIGN: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up. SETTING: Seven SHCS centres. PARTICIPANTS: Patients aged at least 45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at 2-year follow-up of whom 644 had complete data sets. INTERVENTION: Standardized neuropsychological assessment at baseline and 2-year follow-up. MAIN OUTCOME MEASURE: Neurocognitive performance using Frascati criteria and mean z-scores. RESULTS: Four participants (of 644, 0.6%) had plasma HIV-1 RNA more than 50 copies/ml; median CD4+ cell count was 660 cells/µl. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over 2 years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age at least 65 years (P = 0.02) and cognitive complaints (P = 0.004) were associated with neurocognitive decline, while black race (P = 0.01) and dolutegravir treatment (P = 0.002) were associated with improvement. CONCLUSION: Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement.

Fitness-to-drive for glioblastoma patients: Guidance from the Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM).

OBJECTIVE: The management of brain tumour patients who would like to resume driving is complex, and needs multidisciplinary input and a consensus among treating physicians. The Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM) aim to provide guidance on how to assess "fitness-to-drive" of glioblastoma patients and to harmonise the relevant procedures in Switzerland. METHODS: At several meetings, Swiss neuro-oncologists discussed common practices on how to advise patients with a stable, i.e., non-progressive, glioblastoma, who wish to resume driving after the initial standard tumour treatment. All participants of the SwissNOS meetings were invited twice to return a questionnaire (modified Delphi process) on specific tools/procedures they commonly use to assess "fitness-to-drive" of their patients. Answers were analysed to formulate a tentative consensus for a structured and reasonable approach. RESULTS: Consensus on minimum requirements for a "fitness-to-drive" programme for glioblastoma patients could be reached among Swiss neuro-oncologists. The recommendations were based on existing guidelines and expert opinions regarding patients with seizures, visual disturbances, cognitive impairment or focal deficits for safe driving. At this point in time, the Swiss neuro-oncologists agreed on the following requirements for glioblastoma patients after the initial standard therapy and without a seizure for at least 12 months: (1) stable cranial magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria, to be repeated every 3 months; (2) thorough medical history, including current or new medication, a comprehensive neurological examination at baseline (T0) and every 3 months thereafter, optionally an electrocencephalogram (EEG) at baseline; (3) ophthalmological examination including visual acuity and intact visual fields; and (4) optional neuropsychological assessment with a focus on safe driving. Test results have to be compatible with safe driving at any time-point. Patients should be informed about test results and optionally sign a document. CONCLUSIONS: We propose regular thorough clinical neurological examination and brain MRI, optional EEG, neuropsychological and visual assessments to confirm "fitness-to-drive" for glioblastoma patients after initial tumour-directed therapy. The proposed "fitness-to-drive" assessments for glioblastoma patients serves as the basis for a prospective Swiss Pilot Project GLIODRIVE (BASEC ProjectID 2020-00365) to test feasibility, adherence and safety in a structured manner for patients who wish to resume driving. Research will focus on confirming the usefulness of the proposed tools in predicting "fitness-to-drive" and match results with events obtained from the road traffic registry (Strassenverkehrsamt).

[Home infusion therapy for Pompe disease: Recommendations for German-speaking countries]. / Heiminfusionstherapie bei Morbus Pompe: Konsensusempfehlungen für den deutschsprachigen Raum.

BACKGROUND: Pompe disease is a lysosomal multisystem disorder with predominant proximal myopathy. Treatment with enzyme replacement therapy (ERT) is available requiring life-long biweekly infusions of recombinant α-glucosidase. To minimize the burden of ERT patients ask for home infusion therapy. AIMS AND METHODS: Pompe disease experts from Germany, Austria, and Switzerland discussed in two consensus meetings in 2019 and 2020 requirements for home infusion therapy, adequate execution of treatment, and the legal situation for delegating physicians. RESULTS AND DISCUSSION: Home infusion therapy is principally feasible for patients with Pompe disease if certain preconditions are fulfilled, but the decision to implement has to be made on an individual basis. The treating physician delegates the execution of ERT ad personam to nursing staff but retains full legal responsibility. Home infusion therapy has to be carried out by specially trained and qualified staff. Infusion-related risks comprise mainly allergic reactions, and adequate medical treatment must be warranted. In German-speaking countries, clear rules for conducting home infusion therapy are needed to reduce psychosocial stress for patients with Pompe disease, and providing legal certainty for delegating physicians.