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Background Low-grade gliomas (LGGs) represent children’s most prevalent central nervous system tumor, necessitating molecular profiling to diagnose and determine the most suitable treatment. Developing highly sensitive screening techniques for liquid biopsy samples is particularly beneficial, as it enables the early detection and molecular characterization of tumors with minimally invasive samples. Methods We examined CSF and plasma samples from patients with pilocytic astrocytoma (PA) using custom multiplexed droplet digital polymerase chain reaction (ddPCR) assays based on whole genome sequencing data. These assays included a screening test to analyze BRAF duplication and a targeted assay for the detection of patient-specific KIAA1549::BRAF fusion junction sequences or single nucleotide variants. Results Our findings revealed that 5 out of 13 individual cerebrospinal fluid (CSF) samples tested positive for circulating tumor DNA (ctDNA). Among these cases, 3 exhibited the KIAA1549::BRAF fusion, which was detected through copy number variation (CNV) analysis (n = 1) or a fusion-specific probe (n = 2), while 1 case each displayed the BRAF V600E mutation and the FGFR1 N577K mutation. Additionally, a quantitative analysis of cell-free DNA (cfDNA) concentrations in PA CSF samples showed that most cases had low cfDNA levels, below the limit of detection of our assay (<1.9 ng). Conclusions While CNV analysis of CSF samples from LGGs still has some limitations, it has the potential to serve as a valuable complementary tool. Furthermore, it can also be multiplexed with other aberrations, for example, to the BRAF V600 test, to provide important insights into the molecular characteristics of LGGs.

Medulloblastoma is one of the most common types of brain tumors in children. During and after treatment with surgery, chemotherapy, and/or radiotherapy, children with this disease are monitored with imaging and cerebrospinal fluid analysis for the detection of tumor cells. These methods are not always sensitive or specific enough to confirm or rule out residual disease. Here, we develop a laboratory test based on the genetic makeup of medulloblastomas in 12 children. We analyze liquid biopsies (cerebrospinal fluid and blood plasma) for specific genetic fragments leaking from the individual tumors and find molecular traces of disease in 75% (9/12) of children overall. None of the children had malignant cells in the cerebrospinal fluid. We propose that this test could open up new technical possibilities to track measurable residual disease in children with medulloblastoma in order to further risk-adapt treatment, but first, larger studies of the approach at standardized time points are warranted.Medulloblastoma is a malignant embryonal tumor of the central nervous system (CNS) that mainly affects infants and children. Prognosis is highly variable, and molecular biomarkers for measurable residual disease (MRD) detection are lacking. Analysis of cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) using broad genomic approaches, such as low-coverage whole-genome sequencing, has shown promising prognostic value. However, more sensitive methods are needed for MRD analysis. Here, we show the technical feasibility of capturing medulloblastoma-associated structural variants and point mutations simultaneously in cfDNA using multiplexed droplet digital PCR (ddPCR). Assay sensitivity was assessed with a dilution series of tumor in normal genomic DNA, and the limit of detection was below 100 pg of input DNA for all assays. False positive rates were zero for structural variant assays. Liquid biopsies (CSF and plasma, n = 47) were analyzed from 12 children with medulloblastoma, all

Barnneurokirurgi är en subspecialitet inom neurokir­urgin. Barnens neurokirurgiska sjukdomar skiljer sig från de vuxnas med andra diagnoser, patofysiologiska mekanismer, tumörtyper och inte minst annan prognos. I denna artikel belyser vi de tre vanligaste barnneurokirurgiska tillstånden: hjärntumörer, hydrocefalus samt neuralrörsdefekter inklusive ryggmärgsbråck. Vi sammanfattar bakgrund, symtombild och initial handläggning samt ger en översikt av neurokirurgisk behandling av sjukdomarna. Prognosen är oftast god, men samtliga tillstånd är allvarliga och både sjukdom och behandling riskerar att ge livslånga konsekvenser för individen och dess anhöriga.

Introduction: We evaluated salient initiatives invested in global neurosurgery over a 60-year period. Research question: What are the Phases, Achievements, Challenges, and Lessons of Global Neurosurgery. Methods: A 60-year retrospective study from 1960 to 2020 analyzing the major phases, lessons, and progress notes. We reviewed the foundational need questions and innovated tools used to answer them. Results: Three phases defining our study period were identified. In the early phase, birthing academic units and the onset of individual volunteerism were dominant concepts. The 2nd phase is summarized by the rise of volunteerism and surgical camps. The third phase is heralded by advocacy and strategies for achieving care equity.The defining moment is the Lancet commission for global surgery summit in 2015. Lessons include the need for evaluation of the resources of recipient and donor locations using novel global surgery tools. Conclusion: Global neurosurgery over the 60-year study period is summarized by indelible touchstones of personal and group efforts as well as triumphs derived from innovations in the face of formidable challenges.

Background: The COVID-19 pandemic confronts healthcare workers, including neurosurgeons, with difficult choices regarding which patients to treat. Methods: In order to assist ethical triage, this article gives an overview of the main considerations and ethical principles relevant when allocating resources in times of scarcity. Results: We discuss a framework employing four principles: prioritizing the worst off, maximizing benefits, treating patients equally, and promoting instrumental value. We furthermore discuss the role of age and comorbidity in triage and highlight some principles that may seem intuitive but should not form a basis for triage. Conclusions: This overview is presented on behalf of the European Association of Neurosurgical Societies and can be used as a toolkit for neurosurgeons faced with ethical dilemmas when triaging patients in times of scarcity.

Background: DBS (deep brain stimulation) is currently the golden standard in the surgical treatment of ET (essential tremor). Despite the benefits of DBS, there remain situations where lesional surgery may provide an alternative. Objective: To perform a very long-term retrospective evaluation of thalamotomies for ET. Methods: Nine patients who underwent thalamotomy for ET during 1972–1999 (follow-up period 20.8 ± 5.2 years) were assessed with regard to tremor scores, side effects, and quality of life, as well as lesion size and location. Results: All patients had tremor recurrence, although hand function remained slightly better on the treated side than on the non-treated side. Side effects that could be attributed to the procedure were frequent and did in some cases result in a disability for the patient. Quality of life was poorer in this group than in an age-adjusted healthy population. No correlation between lesion size, location, and long-term outcome could be established. Conclusions: In this study population the benefits of thalamotomies were limited, while complications were frequent., Originally published in thesis in manuscript form.

Background: The ventrolateral thalamus (Vim, ventral intermediate nucleus) is the traditional target for neurosurgical treatment of essential tremor (ET). The target has, however, varied substantially among different neurosurgeons. Objective: To evaluate the effect of deep brain stimulation (DBS) in the thalamus and posterior subthalamic area (PSA) in relation to electrode location. Methods: 36 (17Vim / 19 PSA) patients, with 44 DBS electrodes, were included in this retrospective study. The effect of stimulation was evaluated with standardized settings for each contact using items from the essential tremor rating scale (ETRS). Results: When each contact was evaluated regarding the treated hand with standardized stimulation, the electrode contact providing the best effect in the individual patient was in 54% located in the zona incerta (Zi) or radiation prelemniscalis (raprl) and in 12 % the Vim. 40 contacts provided a tremor reduction of >90%. Of these, 43% were located in the PSA and 18% in the Vim according to the Schaltenbrandt atlas. 37 of these 40 contacts were found in the PSA group. Conclusion: More contacts yielding an optimal effect were found in the PSA group than in the Vim. Many patients operated upon in the Vim got the best effect in a contact located in the PSA. This might suggest that the PSA is a more efficient target than the Vim.

The movement disorder essential tremor (ET) has been treated in the past with thalamotomy, a surgical treatment known to cause dysarthria as a side effect. The aim of the current study was to evaluate speech and voice of a group of patients who underwent thalamotomy for ET more than 10 years ago and to determine whether any problems could be linked to the size and laterality of the surgical lesion. Eight patients treated with thalamotomy for ET from 1981 to 1996 participated in a voice and speech evaluation. Patient audio recordings were analyzed perceptually and acoustically, and the patients also self-assessed their speech. Of the eight patients, three were found to have both speech and voice problems, an additional three had only voice problems, and one had an isolated speech rate problem. Three patients reported subjective symptoms. The pattern of occurrence of impairments showed no clear link to the laterality or size of the lesion. It is argued that impaired articulation was likely to have been a consequence of the thalamotomy. However, the finding of voice quality problems was confounded by the disease itself and the patients' ages and thus was probably less likely to be related to the thalamotomy.

The introduction of thalamotomy in 1954 led naturally to exploration of the underlying subthalamic area, with the development of such procedures as campotomy and subthalamotomy in the posterior subthalamic area. The most popular of these procedures was the subthalamotomy, which was performed in thousands of patients for various movement disorders. Today, in the deep brain stimulation (DBS) era, subthalamic nucleus DBS is the treatment of choice for Parkinson's disease, whereas thalamic and pallidal DBS are mainly used for nonparkinsonian tremor and dystonia, respectively. The interest in DBS in the posterior subthalamic area has been quite limited, however, with a total of 95 patients presented in 14 articles. During recent years, interest has increased, and promising results have been published concerning both Parkinson's disease and nonparkinsonian tremor. We reviewed the literature to investigate the development of surgery in the posterior subthalamic area from the lesional era to the present.