Encephalocraniocutaneous lipomatosis phenotype associated with mosaic biallelic pathogenic variants in the NF1 gene.

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic congenital condition characterised by ocular, cutaneous and central nervous system involvement. Mosaic activating variants in FGFR1 and KRAS have been reported in several individuals with this syndrome. We report on a patient with neurofibromatosis type 1 (NF1) with a germline pathogenic variant in the NF1 gene and an ECCL phenotype, suggesting ECCL to be part of a spectrum of malformations associated with NF1 pathogenic variants. An anatomical hemispherectomy was performed for intractable epilepsy. Through genetic analysis of blood, cerebral tissue and giant cell lesions in both jaws, we identified the germline NF1 pathogenic variant in all samples and a second-hit pathogenic NF1 variant in cerebral tissue and both giant cell lesions. Both NF1 variants were located on different alleles resulting in somatic mosaicism for a biallelic NF1 inactivation originating in early embryogenesis (second-hit mosaicism or Happle type 2 mosaicism). The biallelic deficit in NF1 in the left hemicranium explains the severe localised, congenital abnormality in this patient. Identical first and second-hit variants in a giant cell lesion of both upper and lower jaws provide confirmatory evidence for an early embryonic second hit involving at least the neural crest. We suggest that the ECCL phenotype may be part of a spectrum of congenital problems associated with mosaic NF1 nullisomy originating during early embryogenesis. The biallelic NF1 inactivation during early embryogenesis mimics the severe activation of the RAS-MAPK pathway seen in ECCL caused by embryonic mosaic activating FGFR1 and KRAS variants in the cranial region. We propose that distinct mechanisms of mosaicism can cause the ECCL phenotype through convergence on the RAS-MAPK pathway.

Active and Passive Cycling Decrease Subthalamic ß Oscillations in Parkinson's Disease.

BACKGROUND: Preserved cycling capabilities in patients with Parkinson's disease, especially in those with freezing of gait are still poorly understood. Previous research with invasive local field potential recordings in the subthalamic nucleus has shown that cycling causes a stronger suppression of ß oscillations compared to walking, which facilitates motor continuation. METHODS: We recorded local field potentials from 12 patients with Parkinson's disease (six without freezing of gait, six with freezing of gait) who were bilaterally implanted with deep brain stimulation electrodes in the subthalamic nucleus. We investigated ß (13-30 Hz) and high γ (60-100 Hz) power during both active and passive cycling with different cadences and compared patients with and without freezing of gait. The passive cycling experiment, where a motor provided a fixed cadence, allowed us to study the effect of isolated sensory inputs without physical exercise. RESULTS: We found similarly strong suppression of pathological ß activity for both active and passive cycling. In contrast, there was stronger high γ band activity for active cycling. Notably, the effects of active and passive cycling were all independent of cadence. Finally, ß suppression was stronger for patients with freezing of gait, especially during passive cycling. CONCLUSIONS: Our results provide evidence for a link between proprioceptive input during cycling and ß suppression. These findings support the role of continuous external sensory input and proprioceptive feedback during rhythmic passive cycling movements and suggest that systematic passive mobilization might hold therapeutic potential. © 2023 International Parkinson and Movement Disorder Society.

Identifying new predictive factors for survival after surgery for spinal metastases: an exploratory in-depth retrospective analysis.

OBJECTIVES: In selected patients with symptomatic spinal metastasis from solid tumors, surgery improves quality of life. Since selection is key, inaccurate survival prognostication may result in poor decisions and outcomes. However, most prognostic scores suffer from suboptimal external validation and subsequent mediocre performance. This warrants the ongoing search for factors that better capture the oncological status. This exploratory study aims to identify new preoperative variables that predict survival. METHODS: A retrospective analysis was conducted on 62 patients from a tertiary care referral center who underwent debulking and/or reconstruction surgery for spinal metastases between 2006 and 2018, and in whom detailed clinical, oncological, surgical and biochemical variables were collected. Univariate and multivariate analyses were performed for overall survival. RESULTS: Median survival was 13.2 months. Multivariate analysis for overall survival identified that a higher number of organs with metastases, a shorter time to progression on the last line of systemic therapy before surgery (TTPbs), low serum albumin, high alkaline phosphatase, high C-reactive peptide (CRP), presence of brain metastasis and the index spinal level located in the cervical region were independently associated with shorter survival. CONCLUSION: We confirmed previously known predictors and identified CRP and TTPbs as new variables that were strongly associated with survival. The latter variable may replace primary tumor type, as improved cancer treatments make the primary tumor type less relevant as a predictor. This study is exploratory and its findings need to be validated, preferably in large prospective multicenter studies that are aiming at improving existing models.

A most unusual diagnosis via an unusual route: tunneling through Meckel's cave.

A 73-year-old woman presented with progressive symptoms of cranial nerve (V, VI, VIII) palsies, ataxia and gait disturbance due to a rapidly growing atypical trigeminocavernous mass. Percutaneous stereotactic transoval biopsy via Hartel's route revealed an exceedingly rare solitary trigeminal metastasis of a clear cell renal cell carcinoma, treated 16 years earlier without any other evidence of systemic disease. A minimally invasive, intra-operatively navigated approach is presented with detailed description of the stereotactic technique and technical considerations. The transoval biopsy expands the surgical repertoire for atypical Meckel cave lesions with diagnostic uncertainty. A frameless navigated technique should be state-of-the-art in contemporary neurosurgical practice.

Case Report: Initial Evidence of Safety and Efficacy of High Definition-Transcranial Direct Current Stimulation in a Patient With Neuropathic Pain and Implanted Spinal Cord Stimulator.

Neuropathic pain (NP), often treatment-refractory, is one of the most debilitating conditions contributing to suffering and disability worldwide. Recently, non-invasive neuromodulation techniques, particularly repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have emerged as potential therapeutic alternatives due to their ability to alter cortical excitability of neural circuits. However, the magnetic field induced in rTMS may be unsafe for patients with an implanted electrode in the head or neck area while tDCS poses no theoretical risk of injury to these patients. High definition (HD)-tDCS is a novel, more focal technique of tDCS and may be safer to the patient compared to the more diffuse stimulation of conventional tDCS. To our knowledge, no study has ever demonstrated the safety and/or feasibility of HD-tDCS in patients with spinal cord stimulation (SCS) devices using computational modeling of induced electrical fields. Furthermore, this study highlights the potential use of (HD-)tDCS as predictive tool for a positive response in chronic epidural motor cortex stimulation (MCS), especially in patients with an implanted device not suitable for rTMS. In a 54-year-old woman with an implanted spinal cord stimulation (SCS) system for another pain syndrome, HD-tDCS was initiated for refractory post-surgical inferior alveolar nerve neuropathy. She was submitted to 7 days of anodal HD-tDCS over the left motor cortex at 1.5 mA for 30 min. A notable decrease in pain perception was observed, lasting for approximately 5-6 h (Numeric Rating Score decreased from 8 to 4.34). No adverse events were reported. The stimulation parameters and clinical efficacy of the SCS system remained unchanged. Additionally, computational analysis indicated no meaningful alteration of current flow when considering a model with a SCS implant with respect to a model without implant. Regarding the positive therapeutic effect of HD-tDCS, the patient was selected for an epidural MCS trial and subsequent implantation, which showed short-term pain relief of 50-75%. Although one case does not demonstrate efficacy, tolerability, or safety to the novel intervention, it paves the way for better diagnosis and treatment for patients who are otherwise excluded from other non-invasive neuromodulation techniques, such as rTMS. A positive tDCS effect could be a potential biomarker for positive epidural MCS response in patients with an implanted stimulation device non-compatible with rTMS.

Computed tomography based assessment of programmable shunt valve settings.

Introduction: Programmable shunt valve settings can sometimes be difficult to assess using classic read-out tools, warranting a skull X-ray. Research question: Can we use available head computed tomography (CT) scans to determine the valve settings, in order to obviate the need for additional skull X-rays? Material and methods: The valve setting of two different programmable shunts (Codman Certas Plus® and Sophysa Polaris®) were assessed by two blinded observers in 24 patients using 65 head CT scans (slice thickness ≤2 â€‹mm). Using multi-planar reconstruction (MPR) tools, images were resliced according to the direction of the valve, allowing a direct readout of the valve settings. We validated our CT based method against 32 available skull X-rays. Results: For all CT scans it was possible to assess the valve setting. No interobserver variability was found and there was a 100 â€‹% concordance between the CT based method and skull X-rays. Discussion: CT based assessment of programmable shunt valve settings is feasible and reliable. It may obviate the need for additional skull x-rays when a head CT scan is available. Conclusions: This technique can reduce radiation exposure and can be applied to historical CT imaging with unknown valve settings.