EP-0999: Re-irradiation ± bevacizumab in recurrent or progressive HGG: retrospective analysis of 13 patients

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Swiss national guideline for reimbursement of enzyme replacement therapy in late-onset Pompe disease.

Glycogen storage disease type II is a rare multi-systemic disorder characterised by an intracellular accumulation of glycogen due a mutation in the acid alpha glucosidase (GAA) gene. The level of residual enzyme activity, the genotype and other yet unknown factors account for the broad variation of the clinical phenotype. The classical infantile form is characterised by severe muscle hypotonia and cardiomyopathy leading to early death. The late-onset form presents as a limb girdle myopathy with or without pulmonary dysfunction. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) in infants is life saving. In contrast, therapeutic efficacy of rhGAA in the late-onset form is modest. High expenses of rhGAA, on-going infusions and poor pharmacokinetic efficacy raised a discussion of the cost effectiveness of ERT in late-onset Pompe disease in Switzerland. This discussion was triggered by a Swiss federal court ruling which confirmed the reluctance of a health care insurer not to reimburse treatment costs in a 67-year-old female suffering from Pompe disease. As a consequence of this judgement ERT was stopped by all insurance companies in late-onset Pompe patients in Switzerland regardless of their clinical condition. Subsequent negotiations lead to the release of a national guideline of the management of late-onset Pompe disease. Initiation and limitation of ERT is outlined in a national Pompe registry. Reimbursement criteria are defined and individual efficacy of ERT with rhGAA is continuously monitored

Hot Topics on COVID-19 and Its Possible Association with Guillain-Barré Syndrome

As the COVID-19 pandemic progresses, reports of neurological manifestations are increasing. However, despite a high number of case reports and case series on COVID-19 and Guillain-Barré-Syndrome (GBS), a causal association is still highly debated, due to the lack of case-control studies. In this opinion paper, we focus on a few clinically relevant questions regarding the possible link between GBS and SARS-CoV-2 infection or vaccination based on our personal clinical experience and literature review

Radiation-Induced Cavernoma after Total Body Irradiation and Haematopoietic Stem Cell Transplantation in an Adult Patient Suffering from Acute Myeloid Leukaemia

Cerebral cavernomas are thin-walled vascular lesions composed of dilated capillary spaces. De novo formation of cavernomas after cerebral radiotherapy has been suspected since 1994. They are mostly seen in children after irradiation of brain tumours. Radiation dose and the developing juvenile brain are predisposing factors causing cavernomas. However, the underlying mechanisms are still far from being understood. In adults, radiation-induced cavernomas (RICs) usually occur 10 years after a high cumulative radiation dosage of >30 Gy. Here, we report a 45-year-old man with new-onset focal epileptic seizures caused by a haemorrhagic lesion noted on cerebral computed tomography scan. Brain MRI showed the typical appearance of a ruptured cavernoma. Of note, a cerebral MRI scan 5 years earlier showed no corresponding lesion. The patient had been treated with haematopoietic stem cell transplantation for acute myeloid leukaemia (AML) 16 years before. As part of this procedure, total body irradiation (TBI) consisting of 12 Gy was administered. According to the data from the literature, the typical delay from irradiation and a former normal brain MRI scan, we assume that our patient suffers from a RIC. To our knowledge, this is the first documented adult AML patient with a RIC treated with TBI. We aim to increase awareness among neurologists for the association of cranial irradiation or TBI and de novo cavernomas in patients suffering from malignant diseases

Плейотропный нейропротективный и метаболический эффекты актовегина

В обзоре рассматриваются механизмы действия актовегина в контексте изучения его эффектов на доклиническом уровне и новой концепции фармакологического лечения неврологических расстройств. Актовегин, получаемый при ультрафильтрации крови телят, состоит из более чем 200 биологических субстанций. Препарат используется при широком спектре заболеваний, включая нарушения периферического и мозгового кровообращения, ожоги, плохое заживление ран, радиационные поражения и диабетическую полинейропатию. Актовегин состоит из молекул малого размера, которые находятся в организме в нормальных физиологических условиях, и поэтому исследования их фармакокинетики и фармакодинамики для определения активной субстанции препарата затруднены. Результаты преклинических исследований показали, что актовегин улучшает метаболический баланс путем повышения усвоения глюкозы и потребление кислорода в условиях ишемии. Актовегин также повышает устойчивость к гамма-радиации и стимулирует ранозаживление. В более поздних работах было установлено, что антиоксидантный и антиапоптотический механизмы действия лежат в основе нейропротективных свойств актовегина, подтвержденных в экспериментах на первичных нейронах гиппокампа крыс и стрептозотоцининдуцированной модели диабетической полинейропатии у крыс. Последние данные свидетельствуют о положительном влиянии актовегина на фактор NF-κB, но при этом многие молекулярные и клеточные механизмы его действия остаются неизвестными. В первую очередь это касается влияния актовегина на нейропластичность, нейрогенез и трофическую функцию нервной системы, и данный аспект требует дальнейших исследований. Тем не менее становится очевидным, что мультифакториальная и многокомпонентная природа актовегина определяет его плейотропный нейропротективный механизм действия и клиническую эффективность

Intravascular Lymphoma Mimicking Cerebral Stroke: Report of Two Cases

Ischemic stroke is a serious disease leading to significant morbidity and mortality. Multifocal and recurrent strokes are usually caused by embolic diseases, i.e. atrial fibrillation, but rare causes like cerebral vasculitis and clotting disorders are also well known. Here we report on two patients suffering from the very rare intravascular large B-cell lymphoma leading to multifocal and recurrent strokes in the brain and spinal cord as the prominent neurological symptom. The difficulties and the need for diagnostic brain biopsy in making an ‘in vivo’ diagnosis in this particular disease are outlined. Furthermore, the prerequisite for an interdisciplinary approach in these patients is strongly emphasized. Delayed diagnosis for several reasons was the most probable cause for cerebral relapse leading to death in one patient a few months after diagnosis. Conversely, early initiation of immunochemotherapy with a classical lymphoma schedule (R-CHOP) led to long-lasting remission of the disease in the other patient. With this report we like to improve alertness to intravascular large B-cell lymphoma as a cause for multifocal and recurrent strokes

Fingolimod and tumor-infiltrating lymphocytes in checkpoint-inhibitor treated cancer patients.

Immune checkpoint inhibitors (ICIs) are emerging as the new standard of care for treating various metastatic cancers. It is known that effective anti-tumor immune responses are associated with a stronger presence of tumor-infiltrating lymphocytes (TILs) in solid tumor tissue. Cancer patients with relapsing-remitting multiple sclerosis (RRMS) are often under continuous treatment with fingolimod, an immune-modulating drug that inhibits lymphocyte egress from secondary lymphatic organs. Little is known about the effect of fingolimod on ICI cancer therapy, as fingolimod may limit the number of TILs. Here we present three patients with RRMS, who developed various cancers during fingolimod treatment. Histology of all tumors consistently showed low numbers of TILs. A second biopsy taken from one of the tumors, a melanoma, revealed a significant increase of TILs after stopping fingolimod and starting pembrolizumab, indicating a surge in the number and re-invigoration of T cells. Our study suggests that fingolimod limits the number of TILs in solid tumors and may, thus, inhibit anti-cancer immune responses

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