Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses.

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.

Factors affecting ventriculoperitoneal shunt revision: a post hoc analysis of the British Antibiotic and Silver Impregnated Catheter Shunt multicenter randomized controlled trial.

OBJECTIVE: The British Antibiotic and Silver Impregnated Catheter Shunt (BASICS) trial established level I evidence of the superiority of antibiotic-impregnated catheters in the prevention of infection of newly implanted ventriculoperitoneal shunts (VPSs). A wealth of patient, shunt, and surgery-specific data were collected from trial participants beyond that of the prespecified trial objectives. METHODS: This post hoc analysis of the BASICS survival data explores the impact of patient age, hydrocephalus etiology, catheter type, valve type, and previous external ventricular drain on the risk of infection or mechanical failure. Time to failure was analyzed using Fine and Gray survival regression models for competing risk. RESULTS: Among 1594 participants, 75 patients underwent revision for infection and 323 for mechanical failure. Multivariable analysis demonstrated an increased risk of shunt infection associated with patient ages < 1 month (subdistribution hazard ratio [sHR] 4.48, 95% CI 2.06-9.72; p < 0.001) and 1 month to < 1 year (sHR 2.67, 95% CI 1.27-5.59; p = 0.009), as well as for adults with posthemorrhagic hydrocephalus (sHR 2.75, 95% CI 1.21-6.26; p = 0.016). Age ≥ 65 years was found to be independently associated with reduced infection risk (sHR 0.26, 95% CI 0.10-0.69; p = 0.007). Antibiotic-impregnated catheter use was also associated with reduced infection risk (sHR 0.43, 95% CI 0.22-0.84; p = 0.014). Independent risk factors predisposing to mechanical failure were age < 1 month (sHR 1.51, 95% CI 1.03-2.21; p = 0.032) and 1 month to < 1 year (sHR 1.31, 95% CI 0.95-1.81; p = 0.046). Age ≥ 65 years was demonstrated to be the only independent protective factor against mechanical failure risk (sHR 0.64, 95% CI 0.40-0.94; p = 0.024). CONCLUSIONS: Age is the predominant risk for VPS revision for infection and/or mechanical failure, with neonates and infants being the most vulnerable.

Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19.

In November 2021, the COVID-19 pandemic death toll surpassed five million individuals. We applied Mendelian randomization including >3,000 blood proteins as exposures to identify potential biomarkers that may indicate risk for hospitalization or need for respiratory support or death due to COVID-19, respectively. After multiple testing correction, using genetic instruments and under the assumptions of Mendelian Randomization, our results were consistent with higher blood levels of five proteins GCNT4, CD207, RAB14, C1GALT1C1, and ABO being causally associated with an increased risk of hospitalization or respiratory support/death due to COVID-19 (ORs = 1.12-1.35). Higher levels of FAAH2 were solely associated with an increased risk of hospitalization (OR = 1.19). On the contrary, higher levels of SELL, SELE, and PECAM-1 decrease risk of hospitalization or need for respiratory support/death (ORs = 0.80-0.91). Higher levels of LCTL, SFTPD, KEL, and ATP2A3 were solely associated with a decreased risk of hospitalization (ORs = 0.86-0.93), whilst higher levels of ICAM-1 were solely associated with a decreased risk of respiratory support/death of COVID-19 (OR = 0.84). Our findings implicate blood group markers and binding proteins in both hospitalization and need for respiratory support/death. They, additionally, suggest that higher levels of endocannabinoid enzymes may increase the risk of hospitalization. Our research replicates findings of blood markers previously associated with COVID-19 and prioritises additional blood markers for risk prediction of severe forms of COVID-19. Furthermore, we pinpoint druggable targets potentially implicated in disease pathology.

Infant hydrocephalus: what valve first?

PURPOSE: To review the use of different valve types in infants with hydrocephalus, in doing so, determining whether an optimal valve choice exists for this patient cohort. METHODS: We conducted (1) a literature review for all studies describing valve types used (programmable vs. non-programmable, valve size, pressure) in infants (≤ 2 years) with hydrocephalus, (2) a review of data from the pivotal BASICS trial for infant patients and (3) a separate, institutional cohort study from Alder Hey Children's Hospital NHS Foundation Trust. The primary outcome was any revision not due to infection. RESULTS: The search identified 19 studies that were included in the review. Most did not identify a superior valve choice between programmable and non-programmable, small compared to ultra-small, and differential pressure compared to flow-regulating valves. Five studies investigated a single-valve type without a comparator group. The BASICS data identified 391 infants, with no statistically significant difference between gravitational and programmable subgroups. The institutional data from our tertiary referral centre did not reveal any significant difference in failure rate between valve subtypes. CONCLUSION: Our review highlights the challenges of valve selection in infant hydrocephalus, reiterating that the concept of an optimal valve choice in this group remains a controversial one. While the infant-hydrocephalic population is at high risk of valve failure, heterogeneity and a lack of direct comparison between valves in the literature limit our ability to draw meaningful conclusions. Data that does exist suggests at present that there is no difference in non-infective failure rate are increasing in number, with the British valve subtypes in infant hydrocephalus, supported by both the randomised trial and institutional data in this study.

Evolution of surgical attitudes to paediatric thalamic tumours: the alder hey experience.

PURPOSE: Attitudes to surgery for paediatric thalamic tumours have evolved due to improved preoperative imaging modalities and the advent of intraoperative MRI (iMRI) as well as enhanced understanding of tumour biology. We review the developments in our local practice over the last three decades with particular attention to the impact of iMRI. METHODS: We identified all paediatric patients from a prospectively maintained neuro-oncology database who received surgery for a thalamic tumour (n = 30). All children were treated in a single UK tertiary paediatric neurosurgery centre between January 1991 and June 2020. Twenty patients underwent surgical resection, the remainder (10) undergoing biopsy only. Pre-operative surgical intent (biopsy versus debulking, near-total resection, or complete resection) as well as the use of iMRI were prospectively recorded. Complications recorded in clinical documentation between postoperative days 0 and 30 were retrospectively graded using a modified version of the Clavien Dindo scale. The extent of resection with respect to the pre-determined surgical aim was also recorded. Data on patient survival and disease progression status were obtained retrospectively. RESULTS: In our series, there were 42 procedures (25 craniotomies, 17 biopsies) performed on 30 patients (17 male, with a median age of 8 at surgery). Of the 25 surgical resections performed, complete resection was achieved in 9 (36%), near-total resection in 10 (40%), and limited debulking in 6 (24%). The predetermined surgical aim was achieved or exceeded in 91.3% of cases. The proportion of craniotomies for which substantial resection was achieved, increased from 37.5 to 94.2% with use of iMRI (p = 0.014). Surgical morbidity was not associated with greater extent of surgical resection. High-grade histology is identified as the only independent significant factor influencing overall survival as calculated by Cox proportional hazards model (p = 0.006). CONCLUSION: We note a significant change in the rate and extent of attempted resection of paediatric thalamic tumours that has developed over the last 3 decades. Use of iMRI is associated with a significant increase in substantial tumour resection surgeries. This is not associated with any significant level of surgical morbidity. Improvements in pre- and intra-operative imaging alongside better understanding of tumour biology facilitate patient selection and a surgically more aggressive approach in selected cases whilst maintaining safety and avoiding operative morbidity.

Neurosurgical CSF Diversion in Idiopathic Intracranial Hypertension: A Narrative Review.

The prevalence of idiopathic intracranial hypertension (IIH), a complex disorder, is increasing globally in association with obesity. The IIH syndrome occurs as the result of elevated intracranial pressure, which can cause permanent visual impairment and loss if not adequately managed. CSF diversion via ventriculoperitoneal and lumboperitoneal shunts is a well-established strategy to protect vision in medically refractory cases. Success of CSF diversion is compromised by high rates of complication; including over-drainage, obstruction, and infection. This review outlines currently used techniques and technologies in the management of IIH. Neurosurgical CSF diversion is a vital component of the multidisciplinary management of IIH.

Reporting morbidity associated with pediatric brain tumor surgery: are the available scoring systems sufficient?

OBJECTIVE: Complications in pediatric neurooncology surgery are seldom and inconsistently reported. This study quantifies surgical morbidity after pediatric brain tumor surgery from the last decade in a single center, using existing morbidity and outcome measures. METHODS: The authors identified all pediatric patients undergoing surgery for an intracranial tumor in a single tertiary pediatric neurosurgery center between January 2008 and December 2018. Complications between postoperative days 0 and 30 that had been recorded prospectively were graded using appropriate existing morbidity scales, i.e., the Clavien-Dindo (CD), Landriel, and Drake scales. The result of surgery with respect to the predetermined surgical aim was also recorded. RESULTS: There were 477 cases (364 craniotomies and 113 biopsies) performed on 335 patients (188 males, median age 9 years). The overall 30-day mortality rate was 1.26% (n = 6), and no deaths were a direct result of surgical complication. Morbidity on the CD scale was 0 in 55.14%, 1 in 10.69%, 2 in 18.66%, 3A in 1.47%, 3B in 11.74%, and 4 in 1.05% of cases. Morbidity using the Drake classification was observed in 139 cases (29.14%). Neurological deficit that remained at 30 days was noted in 8.39%; 78% of the returns to the operative theater were for CSF diversion. CONCLUSIONS: To the authors' knowledge, this is the largest series presenting outcomes and morbidity from pediatric brain tumor surgery. The mortality rate and morbidity on the Drake classification were comparable to those of published series. An improved tool to quantify morbidity from pediatric neurooncology surgery is necessary.

Patient-Reported Outcomes Following Lumbar Decompression Surgery: A Review of 2699 Cases.

STUDY DESIGN: Retrospective case series. OBJECTIVE: Despite numerous advances in the technology and techniques available to spinal surgeons, lumbar decompression remains the mainstay of degenerative lumbar spine surgery. It has proven efficacy in trials, but only limited evidence of advantage over conservative management in large scale systematic reviews. We collated data from a large surgically managed cohort to evaluate the patient-reported outcomes. METHODS: We performed a retrospective analysis of a prospectively populated database. Patient demographics, surgical details, and patient outcomes (Spine Tango core outcome measures index [COMI]-Low Back) were collected for 2699 lumbar decompression surgeries. RESULTS: Lumbar decompression was shown to be successful at improving leg pain (mean improvement in visual analogue scale [VAS] at 3 months = 4) and to a lesser extent, back pain (mean improvement in VAS at 3 months = 2.61). Mean improvement in COMI score was 3.15 for all-comers. Minimal clinically important improvement (MCID) in COMI score (-2 points) was achieved in 73% of patients by 2-year follow-up. Primary surgery was more effective than redo surgery: odds ratio 0.547 (95% CI 0.408-0.733, P < .001). The benefits across all outcomes were maintained for the 2-year follow-up period. Patients can be classified according to their outcome as "early responders"; achieving MCID by 3 months (61% primary vs 41% redo), "late responders"; achieving MCID by 2 years (15% vs 20%) or nonresponders (24% vs 39%). CONCLUSIONS: Lumbar decompression is effective in improving quality of life in appropriately selected patients. Patient-reported outcome measures collected routinely and collated within a registry are a powerful tool for assessing the efficacy of lumbar spine interventions and allow accurate counseling of patients perioperatively.

Re-Exploration of Microvascular Decompression in Recurrent Trigeminal Neuralgia and Intraoperative Management Options.

BACKGROUND: Trigeminal neuralgia (TGN) is a debilitating disorder, and in patients for whom medical management is not sufficient, there are several therapeutic options. Microvascular decompression (MVD) for TGN has been shown to be highly effective; however, pain does recur after MVD in some patients. Therapeutic options for recurrent TGN are the same as those for primary TGN, including re-exploration of MVD (re-MVD). In this study we review our practice of re-MVD, comparing it with alternative options and assessing its safety and efficacy. METHODS: Retrospective analysis of prospectively collected data of patients undergoing re-MVD between 2007 and 2016. RESULTS: Thirty-two patients underwent re-MVD, all with a Barrow Neurosurgical Institute Pain Index (BNPI) of IV or V. Postoperatively, 87% of patients reported an improvement in their BNPI to III or better, with 50% being BNPI 1 or 2. Eleven patients without distortion or vascular conflict at the time of re-exploration underwent intraoperative neurolysis, and 90% reported improvement in their BNPI. Kaplan-Meier analysis showed a median pain-free period of 36 months after re-MVD. There were no significant complications. CONCLUSIONS: Re-MVD is a safe and effective method of treating recurrent TGN. Intraoperative neurolysis is an important tool in re-exploration and should be considered when there is no ongoing compression or distortion of the trigeminal nerve.

Surgical management of posterior fossa metastases.

The diagnosis of brain metastases is associated with a poor prognosis reflecting uncontrolled primary disease that has spread to the relative sanctuary of the central nervous system. 20 % of brain metastases occur in the posterior fossa and are associated with significant morbidity. The risk of acute hydrocephalus and potential for sudden death means these metastases are often dealt with as emergency cases. This approach means a full pre-operative assessment and staging of underlying disease may be neglected and a proportion of patients undergo comparatively high risk surgery with little or no survival benefit. This study aimed to assess outcomes in patients to identify factors that may assist in case selection. We report a retrospective case series of 92 consecutive patients operated for posterior fossa metastases between 2007 and 2012. Routine demographic data was collected plus data on performance status, primary cancer site, details of surgery, adjuvant treatment and survival. The only independent positive prognostic factors identified on multivariate analysis were good performance status (if Karnofsky performance score >70, hazard ratio (HR) for death 0.36, 95 % confidence interval (CI) 0.18-0.69), adjuvant whole brain radiotherapy (HR 0.37, 95 % CI 0.21-0.65) and adjuvant chemotherapy where there was extracranial disease and non-synchronous presentation (HR 0.51, 95 % CI 0.31-0.82). Patients presenting with posterior fossa metastases may not be investigated as thoroughly as those with supratentorial tumours. Staging and assessment is essential however, and in the meantime emergencies related to tumour mass effect should be managed with steroids and cerebrospinal fluid diversion as required.

Prostate dural metastasis presenting as chronic subdural hematoma. A case report and review of the literature.

BACKGROUND: Malignant disease metastasising to the cranial dura is rare. Dural metastases manifesting as a subdural fluid collection and presenting as a chronic subdural hematoma is an uncommon entity with unknown pathophysiology. CASE DESCRIPTION: We present a patient with known prostate cancer metastasising to the cranial dura masquerading as a chronic subdural hematoma. The patient presented with bilateral subdural collections manifesting with confusion and dysphasia. Initial drainage of the larger, symptomatic left side improved only temporarily patient's symptoms. A second drainage of the collection was performed on the same side 5 days later and dural biopsies taken during the same procedure revealed prostate metastases. The patient improved slowly and was discharged to a hospice for palliative care management. CONCLUSIONS: Prostate dural metastases should be suspected in patients with known prostate cancer presenting with a subdural collection in the absence of cranial trauma. If decision to drain the subdural collection is taken, then biopsies can be taken the same time as they can pose a diagnostic challenge.

Development of anterior inferior cerebellar artery pseudoaneurysm after gamma knife surgery for vestibular schwannoma. A case report and review of the literature.

Gamma knife surgery (GKS) is a well-established modality for controlling the progression of vestibular schwannomas. Adverse effects of this treatment are extremely rare but include cyst formation and malignant transformation. We report a case of anterior inferior cerebellar artery (AICA) pseudoaneurysm development rupture presenting as a poor WFNS grade subarachnoid haemorrhage. This is only the fourth case of aneurysm development (AICA aneurysm) following GKS reported but due to its serious nature we believe this potential complication warrants awareness in those offering this treatment.