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Paediatric high-grade gliomas (pedHGGs) are highly invasive brain tumours accounting for approximately 15 % of all central nervous system (CNS) tumours in children and adolescents. The outcome for these tumours is generally poor with 5-year survival rates of less than 20 %. Despite improved biological insights into pedHGGs and the promise of more effective therapies, little progress has been made in the effective treatment and the outcome of these tumours over the last four decades. Much of the evidence for the use of chemotherapy in pedHGGs is extrapolated from adult data, and the evidence for its use in the paediatric population is still weak. This guideline was written by members of the SIOPE HGG Working Group as part of the European Standard Clinical Practice (ESCP) Project of the European Reference Network for Paediatric Oncology, ERN PaedCan. The guideline aims to integrate available evidence-based and expert opinion-based information to assist healthcare professionals in the management of pedHGGs and in an attempt to provide equity in healthcare reflecting the varying resources of each European country.

White matter (WM) disruption and atrophy is a consequence of traumatic brain injury (TBI) and contributes to persisting cognitive impairment. An increased expression of the myelin-associated axonal outgrowth inhibitor Nogo-A and oligodendrocyte pathology might be negatively associated with postinjury WM changes. Here, we analyzed brain tissue from severe TBI patients, obtained by surgical decompression in the early postinjury phase and postmortem brain tissue of long-term TBI survivors and observed an increased number of Nogo-A⁺ cells in WM tracts such as the corpus callosum (CC). Likewise, the number of Nogo-A⁺ cells in the CC was increased from day 7 postinjury to 6 months postinjury (mpi) following central fluid percussion injury (cFPI) in mice. In addition, the number of Olig2⁺ cells in the CC and capsula externa remained constant, while the numbers of Olig2⁺/CC1⁺ and GST-pi⁺ mature oligodendrocytes declined throughout the observation time of 18 months. A significantly lower number of Olig2⁺/CC1⁺ cells was found in cFPI mice compared to controls at 18 mpi. Persistent vulnerability of oligodendrocytes in combination with dynamic alterations of Nogo-A expression may have implications for the WM atrophy and insufficient recovery observed after TBI.

Aim

Hydrocephalus surgery with a ventriculoperitoneal shunt is a life-saving treatment, but it has been associated with a high risk of dysfunction and complications. We investigated whether infants who received a ventriculoperitoneal shunt below 12 months of age had a reduced risk of acute shunt dysfunction if they were included in a structured follow-up programme.

Methods

A population-based, retrospective chart review was performed at Uppsala University Children's Hospital, Sweden. Patients were identified by International Classification of Diseases, Tenth Revision codes and surgical codes from 1 January 2005 to 31 December 2019. Those who received the structured follow-up programme from April 2012 were compared with historical controls.

Results

We identified 95 patients (66% male): 47 in the follow-up group and 48 controls. Their mean age was 2.6 (range 0–12) months. There was a high 44% acute shunt dysfunction rate during the first year after primary surgery: 38% in the follow-up group and 50% in the control group (p = 0.25). The difference was not significant.

Conclusion

The structured follow-up programme was not associated with a significant reduction in acute shunt dysfunction. Predictive models could help to identify patients at risk for shunt dysfunction and complications and improve surveillance and follow-up programmes.

Traumatic brain injury (TBI) often leads to impaired regulation of cerebral blood flow, which may be caused by pathological changes of the vascular smooth muscle cells (VSMCs) in the arterial wall. Moreover, these cerebrovascular changes may contribute to the development of various neurodegenerative disorders such as Alzheimer’s-like pathologies that include amyloid beta aggregation. Despite its importance, the pathophysiological mechanisms responsible for VSMC dysfunction after TBI have rarely been evaluated. Here, we show that acute human TBI resulted in early pathological changes in leptomeningeal arteries, closely associated with a decrease in VSMC markers such as NOTCH3 and alpha smooth muscle actin (α-SMA).These changes coincided with increased aggregation of variable-length amyloid peptides including Aβ_1-40/42, Aβ_1-16, and β-secretase-derived fragment (βCTF) (C99) caused by altered processing of amyloid precursor protein (APP) in VSMCs. The aggregation of Aβ_1-40/42 peptides were also observed in the leptomeningeal arteries of young TBI patients. These pathological changes also included higher β-secretase (BACE1) when compared to α-secretase A Disintegrin And Metalloprotease 10 (ADAM10) expression in the leptomeningeal arteries, plausibly caused by hypoxia and oxidative stress as shown using human VSMCs in vitro. Importantly, BACE1 inhibition not only restored NOTCH3 signalling but also normalized ADAM10 levels in vitro. Furthermore, we found reduced ADAM10 activity and decreased NOTCH3, along with increased βCTF (C99) levels in mice subjected to an experimental model of TBI. This study provides evidence of early post-injury changes in VSMCs of leptomeningeal arteries that can contribute to vascular dysfunction and exacerbate secondary injury mechanisms following TBI.

BACKGROUND: Trigeminal neuralgia (TN) is a severe facial pain condition often associated with a neurovascular conflict. However, neuroinflammation has also been implicated in TN, as it frequently co-occurs with multiple sclerosis (MS).

METHODS: We analysed protein expression levels of TN patients compared to MS patients and controls. Proximity Extension Assay technology was used to analyse the levels of 92 proteins with the Multiplex Neuro-Exploratory panel provided by SciLifeLab, Uppsala, Sweden. Serum and CSF samples were collected from TN patients before (n = 33 and n = 27, respectively) and after (n = 28 and n = 8, respectively) microvascular decompression surgery. Additionally, we included samples from MS patients (n = 20) and controls (n = 20) for comparison.

RESULTS: In both serum and CSF, several proteins were found increased in TN patients compared to either MS patients, controls, or both, including EIF4B, PTPN1, EREG, TBCB, PMVK, FKBP5, CD63, CRADD, BST2, CD302, CRIP2, CCL27, PPP3R1, WWP2, KLB, PLA2G10, TDGF1, SMOC1, RBKS, LTBP3, CLSTN1, NXPH1, SFRP1, HMOX2, and GGT5. The overall expression of the 92 proteins in postoperative TN samples seems to shift towards the levels of MS patients and controls in both serum and CSF, as compared to preoperative samples. Interestingly, there was no difference in protein levels between MS patients and controls.

CONCLUSIONS: We conclude that TN patients showed increased serum and CSF levels of specific proteins and that successful surgery normalizes these protein levels, highlighting its potential as an effective treatment. However, the similarity between MS and controls challenges the idea of shared pathophysiology with TN, suggesting distinct underlying mechanisms in these conditions.

SIGNIFICANCE: This study advances our understanding of trigeminal neuralgia (TN) and its association with multiple sclerosis (MS). By analysing 92 protein biomarkers, we identified distinctive molecular profiles in TN patients, shedding light on potential pathophysiological mechanisms. The observation that successful surgery normalizes many protein levels suggests a promising avenue for TN treatment. Furthermore, the contrasting protein patterns between TN and MS challenge prevailing assumptions of similarity between the two conditions and point to distinct pathophysiological mechanisms.

Trigeminal neuralgia (TN) is a severe facial pain disease of uncertain pathophysiology and unclear genetic background. Although recent research has reported a more important role of genetic factors in TN pathogenesis, few candidate genes have been proposed to date. The present study aimed to identify independent genetic variants in the protein-coding genes associated with TN. We focused on genes previously linked to TN based on the results of four proteomic studies conducted by our research team. The goal was to validate these findings on the genetic level to enhance our understanding of the role of genetics in TN. The study is based on the participants from UK Biobank cohort. Following quality control, 175 independent single nucleotide polymorphisms (SNPs) in 17 genes were selected. The study sample comprised of diagnosed TN cases (N = 555) and randomly matched controls (N = 6245) based on specific criteria. Two SNPs corresponding to C8B rs706484 [odds ratio (OR) (95% confidence interval (CI)): 1.357 (1.158–1.590); p: 0.00016] and MFG-E8 rs2015495 [OR (95% CI): 1.313 (1.134–1.521); p: 0.00028] showed significant positive association with TN, indicating a positive effect of the SNP alleles on gene expression and disease risk. Interestingly, both SNPs are Expression Quantitative Trait Loci (eQTLs), and are associated with changes in the expression activity of their corresponding gene. Our findings suggest novel genetic associations between C8B, a key component of the complement system, and MFG-E8, which plays a role in regulating neuroinflammation, in relation to TN. The identified genetic variations may help explain why some individuals develop TN while others do not, indicating a potential genetic predisposition to the condition.

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.

Background

The primary aim of this observational study was to determine the incidence of trigeminal neuralgia (TN) in a county in central Sweden. The secondary aim was to investigate TN characteristics including the affected side and nerve branches.

Methods

Patients that received the ICD-10 diagnostic codes TN (G50.0), atypical facial pain (G50.1) and other/unspecified disorder of the trigeminal nerve (G50.8 and G50.9) in Uppsala County, between 2009 and 2017, were eligible for inclusion. Case ascertainment was conducted by the authors by review of the medical records.

Results

The incidence of TN was estimated to be 5.5 (95% confidence interval 4.7–6.4) per 100,000 person-years. The incidence increased with age, from 0.1 in 0- to 19-year-olds to 23.1 per 100,000 person-years in 80+-year-olds. Females exhibited a higher incidence at 7.3 than males at 3.7 per 100,000 person-years. Most of the trigeminal neuralgia cases were diagnosed in the Neurology department (47%). Trigeminal neuralgia was most frequently right sided (59%) and limited to one cranial nerve V-branch, of which V2 was the most common.

Conclusions

Trigeminal neuralgia incidence was estimated to be 5.5 per 100,000 person-years. The incidence was higher for females and increased with older age.

Significance

There is limited knowledge about the true incidence of trigeminal neuralgia. This manuscript provides an estimate of 5.5 cases per 100,000 person-years, by using a thorough case ascertainment methodology.

BACKGROUND: Trigeminal neuralgia (TN), a severe type of facial pain, is mainly caused by a neurovascular conflict (NVC). The severity of the NVC seems associated with the outcome following microvascular decompression (MVD) surgery. This study aimed to investigate the outcome after MVD and whether it is affected by NVC severity and sex.

METHODS: TN patients (n = 109) were followed for 5 to 10 years after MVD. Barrow Neurology Index (BNI), Patients Global Impression of Change (PGIC), complications, and time to relapse were evaluated. The NVC severity was retrospectively reviewed from presurgical MRI. Demographic and clinical factors and NVC severity were analyzed for potential association with outcome after MVD.

RESULTS: The success rate (BNI ≤ 2) was 80% after 5 to 10 years follow-up for TN patients with severe NVC (grade 2-3) and 56% for TN patients with mild NVC (grade 0-1, P = 0.003). No sex difference was observed in outcome for patients with both mild (P = 0.924) and severe NVC (P = 0.883) respectively. Three patients (2.8%) during the hospital stay, and two patients (1.8%) at 6 weeks, experienced a complication requiring invasive treatment. At long-term 52/109 patients (47.7%) reported some type of persistent adverse event, of which the majority were mild and required no treatment.

CONCLUSIONS: MVD offers an 80% probability of long-term pain relief in TN patients with severe NVC, with low frequency of serious complications. NVC severity significantly affects outcome after MVD, while no sex differences in outcome were found. In consistency with previous work, the results stress the importance of adequate neuroradiological assessment of the NVC for preoperative patient selection.