The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data From 121 Surgically Treated Participants From the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: An important proportion of patients with spontaneous intracerebral hemorrhage (ICH) undergo neurosurgical intervention to reduce mass effect from large hematomas and control the complications of bleeding, including hematoma expansion and hydrocephalus. The Tranexamic acid (TXA) for hyperacute primary IntraCerebral Hemorrhage (TICH-2) trial demonstrated that tranexamic acid (TXA) reduces the risk of hematoma expansion. We hypothesized that TXA would reduce the frequency of surgery (primary outcome) and improve functional outcome at 90 days in surgically treated patients in the TICH-2 data set. METHODS: Participants enrolled in TICH-2 were randomized to placebo or TXA. Participants randomized to either TXA or placebo were analyzed for whether they received neurosurgery within 7 days and their characteristics, outcomes, hematoma volumes (HVs) were compared. Characteristics and outcomes of participants who received surgery were also compared with those who did not. RESULTS: Neurosurgery was performed in 5.2% of participants (121/2325), including craniotomy (57%), hematoma drainage (33%), and external ventricular drainage (21%). The number of patients receiving surgery who received TXA vs placebo were similar at 4.9% (57/1153) and 5.5% (64/1163), respectively (odds ratio [OR] 0.893; 95% CI 0.619-1.289; P-value = .545). TXA did not improve outcome compared with placebo in either surgically treated participants (OR 0.79; 95% CI 0.30-2.09; P = .64) or those undergoing hematoma evacuation by drainage or craniotomy (OR 1.19 95% 0.51-2.78; P-value = .69). Postoperative HV was not reduced by TXA (mean difference -8.97 95% CI -23.77, 5.82; P-value = .45). CONCLUSION: TXA was not associated with less neurosurgical intervention, reduced HV, or improved outcomes after surgery.

What are the predictors of delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage? An up-to-date systematic review.

PURPOSE: Delayed Cerebral Ischaemia (DCI) remains an important preventable driver of poor outcome in aneurysmal subarachnoid haemorrhage (aSAH). Our ability to predict DCI is based on historical patient cohorts, which use inconsistent definitions for DCI. In 2010, a definition of DCI was agreed upon and published by a group of aSAH experts. The aim of this study was to identify predictors using this agreed definition of DCI. METHODS: We conducted a literature search of Medline (PubMed) to identify articles published since the publication of the 2010 consensus definition. Risk factors and prediction models for DCI were included if they: (1) adjusted for confounding factors or were derived from randomised trials, (2) were derived from prospectively collected data and (3) included adults with aSAH. The strength of studies was assessed based on quality, risk of bias and applicability of studies using PROBAST. RESULTS: Eight studies totalling 4,542 patients were included from 105 relevant articles from 4,982 records. The most common reason for not including studies was failure to use the consensus definition of DCI (75%). No prediction models were identified in the eligible studies. Significant risk factors for DCI included the presence of onsite neuro-interventional services, high Neuropeptide Y, admission leucocytosis, neutrophil:lymphocyte >5.9 and Fisher Grade > 2. All studies had a high or unclear risk of bias. CONCLUSIONS: Only a few studies with high risk of bias have investigated the predictors using consensus-defined DCI. Further studies are warranted to clarify risk factors of DCI in the modern era.

Surgery for Malignant Acute Ischemic Stroke: A Narrative Review of the Knowns and Unknowns.

Malignant acute ischemic stroke (AIS) is characterized by acute neurological deterioration caused by progressive space-occupying brain edema, often occurring in the first hours to days after symptom onset. Without any treatment, the result is often fatal. Despite advances in treatment for AIS, up to 80% of patients with a large hemispheric stroke or cerebellar stroke are at risk of poor outcome. Decompressive surgery can be life-saving in a subgroup of patients with malignant AIS, but uncertainties exist on patient selection, predictors of malignant infarction, perioperative management, and timing of intervention. Although survivors are left disabled, most agree with the original decision to undergo surgery and would make the same decision again. In this narrative review, we focus on the clinical and radiological predictors of malignant infarction in AIS and outline the technical aspects of decompressive surgery as well as duraplasty and cranioplasty. We discuss the current evidence and recommendations for surgery in AIS, highlighting gaps in knowledge, and suggest directions for future studies. KEY POINTS: · Acute ischemic stroke from occlusion of a proximal intracranial artery can progress quickly to malignant edema, which can be fatal in 80% of patients despite medical management.. · Decompression surgery is life-saving within 48 hours of stroke onset, but the benefits beyond this time and in the elderly are unknown.. · Decompressive surgery is associated with high morbidity, particularly in the elderly. The decision to operate must be made after considering the individual's preference and expectations of quality of life in the context of the clinical condition.. · Further studies are needed to refine surgical technique including value of duraplasty and understand the role monitoring intracranial pressure during and after decompressive surgery.. · More studies are needed on the pathophysiology of malignant cerebral edema, prediction models including imaging and biomarkers to identify which subgroup of patients will benefit from decompressive surgery.. · More research is needed on factors associated with morbidity and mortality after cranioplasty, safety and efficacy of implants, and comparisons between them.. · Further studies are needed to assess the long-term effects of physical disability and quality of life of survivors after surgery, particularly those with severe neurological deficits..

Infusion-related side-effects during convection enhanced delivery for brainstem-diffuse midline glioma/diffuse intrinsic pontine glioma.

INTRODUCTION: Side-effects during convection enhanced delivery (CED) are poorly understood. We intended to determine the frequency of side-effects during brain stem infusion and determine risk factors for side-effects persisting longer than 24 h. METHODS: Children with a radiological diagnosis of brain stem diffuse midline glioma/Diffuse Intrinsic Pontine Glioma were treated on compassionate grounds with awake infusion of carboplatin and sodium valproate into the brain stem using the 4-catheter (2 trans-cerebellar 2 trans-frontal) chronic, intermittent Renishaw Drug Delivery System. We used change in the Pontine Neurological Observation Score (PONScore), a standardised neurological assessment tool, to identify side-effects during infusion. Recovery was determined by retrospective chart review. RESULTS: 55 infusions were performed in 8 children (3-11 years). Mean PONScore increased during infusion from 3.3 to 5.7 (p-value > 0.001). One hundred and fifty-seven infusion-related side-effects were identified including headache (33/157) and limb weakness (49/157). Fifty-four side-effects persisted > 24 h. Side-effects that had occurred during a previous infusion and those that occurred during infusion via trans-cerebellar catheters were more likely to be persistent with OR 2.333 (95% CI 1.094-4.976; p-value = 0.028) and 2.155 (1.029-4.513; p-value = 0.042) respectively. If infusion was stopped or titrated at onset rather than continued, the side-effect was less likely to persist > 24 h, OR 0.473 (95% CI 0.177-0.948; p-value = 0.037). Most side-effects developed within the first three millilitre of infusion. CONCLUSIONS: Side-effects during brainstem infusion are common, can be transient or persist longer than 24 h. Neurological injury during infusion may be time dependent and accumulative rather than volume dependent.

Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy.

PURPOSE: Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS). METHODS: Retrospective review (2017-2020) of children with DIPG, who following radiotherapy, received compassionate treatment commencing 3.3-10 months post-diagnosis (median 4.9 months). They received up to 7 cycles of 3-6 weekly pontine infusions of carboplatin (0.12-0.18 mg/ml) and sodium valproate (14.4-28.8 mg/ml). RESULTS: 13 children 3-19 years (mean 6.9 years) were treated. There were no surgical complications. With the exception of infusion channels blocking in one device, there were no adverse device effects. Two patients developed persistent 6th nerve palsies, which led to drug concentration reduction in the combination therapy. Subsequently infusion/ drug-related toxicities were transient. Tumour was controlled in pons in 10/13 patients. Median progression-free survival (PFS) was 13.0 months, while median overall survival (OS) was 15.3 months. CONCLUSIONS: Use of the RDDS was safe and well tolerated in all 13 patients. Treatment improved control of pontine disease resulting in longer PFS and OS and merits further evaluation in a clinical trial.

A case of malignant cerebral infarction associated with COVID-19 infection.

Stroke as a presenting feature of COVID-19 infection is being increasingly recognized. We describe a case of a 46-year-old healthcare worker with COVID-19 who developed malignant cerebral infarction requiring emergency decompressive craniectomy. This case illustrates the neurosurgical implications associated with inflammatory and pro-coagulopathic derangements in COVID-19 disease.

What do neurosurgical trainees think about neuro-interventional training and service provision in the United Kingdom?

BACKGROUND: There is a disparity between the number of interventional neuroradiologists (INRs) in the UK and the number needed to provide a comprehensive 24/7 interventional neurovascular service. It is recognized that trainees from other specialties such as neurosurgery may be able to provide INR services after appropriate training. At present gaining skills in INR is not a mandatory requirement of the neurosurgical training curriculum in the UK. The views on this issue of current neurosurgical trainees are unknown. We aimed to address this knowledge gap. METHODS: We performed an anonymized online survey to gauge the opinion of neurosurgical trainees about their attitudes to INR training and service provision. RESULTS: 90/265 (34%) UK neurosurgical trainees responded to the survey. About 56% of respondents reported they were likely or very likely to pursue interventional training if a curriculum was approved by the general medical council. About 80% thought training should take up to 2 years. About 90% of those very likely or likely to pursue INR wanted a hybrid neurosurgical practice and 92% were willing to provide endovascular services out of hours. CONCLUSION: The responses described suggest that a significant proportion of neurosurgical trainees would pursue INR training and have realistic expectation regarding out of hours commitment and length of training.

Development of a clinical scale for assessment of patients with diffuse intrinsic pontine glioma (DIPG) receiving experimental therapy: the PONScore.

PURPOSE: Monitoring neurological side-effects in experimental therapy for diffuse intrinsic pontine glioma (DIPG) can be challenging. We aimed to develop a neurological scale that could be used by non-specialists to quantify neurological changes during experimental treatment of DIPG. METHODS: We developed the Pontine Observational Neurological Score (PONScore) to measure signs and symptoms of DIPG by adapting validated assessment scales of neurological signs and symptoms in children. We developed a prototype score, taught it to paediatric intensive care nursing staff, who used the Score to assess children receiving awake pontine infusion of chemotherapy for treatment of DIPG. We used their feedback to develop the PONScore. Points are allocated for headache, ophthalmoplegia, facial and tongue weakness, dysarthria, paraesthesia, limb weakness and dysmetria with increasing scores reflecting increasing disability. The PONScore was administered every hour during awake pontine infusion. Correlation and agreement calculations between nursing staff, as non-specialists, and a specialist rater were performed in 30 infusions in 6 children (aged 8-11). Changes in PONScore versus volume of infusion are described in a further 55 infusions in 8 children (aged 3-11). RESULTS: The PONScore demonstrated excellent intra-rater reliability with an intra-class co-efficient of 0.98 (95% CI 0.97-0.99; p-value < 0.001) between a specialist and non-specialist raters with strong correlation between scores and a Spearman correlation coefficient of 0.985 (p < 0.001). PONScores increased from 3.3 to 5.7 (p-value < 0.001) during infusion reflecting accumulation of neurological signs and symptoms during infusion. CONCLUSIONS: We describe a novel neurological scale that can be used by non-specialists to describe acute neurological changes in children receiving experimental therapy for DIPG. Prospective validation as part of a clinical trial is required.

Single Electrode Deep Brain Stimulation with Dual Targeting at Dual Frequency for the Treatment of Chronic Pain: A Case Series and Review of the Literature.

Deep Brain Stimulation (DBS) has been used to target many deep brain structures for the treatment of chronic pain. The periaqueductal grey and periventricular grey (PAG/PVG) is an effective target but results are variable, sometimes short-lived or subject to tolerance. The centromedian intra-laminar parafascicular complex (CMPf) modulates medial pain pathways and CMPf DBS may address the affective aspects of pain perception. Stimulation of multiple deep brain targets may offer a strategy to optimize management of patients with complex pain symptomatology. However, previous attempts to stimulate multiple targets requires multiple trajectories and considerable expense. Using a single electrode to stimulate multiple targets would help overcome these challenges. A pre-requisite of such a technique is the ability to use different stimulation parameters at different contacts simultaneously on the same electrode. We describe a novel technique in 3 patients with chronic pain syndromes for whom conventional medical and/or neuromodulation therapy had failed using a single electrode technique to stimulate PVG/PAG and CMPf at dual frequencies.

Results of an International Survey on the Investigation and Endovascular Management of Cerebral Vasospasm and Delayed Cerebral Ischemia.

BACKGROUND: Delayed cerebral ischemia (DCI) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage. Endovascular management of this condition offers a new hope in preventing adverse outcome; however, a uniform standard of practice is lacking owing to a paucity of clinical trials. We conducted an international survey on the use of investigative and endovascular techniques in the treatment of DCI to assess the variability of current practice. METHODS: Neurovascular neurosurgeons and neuroradiologists were contacted through professional societies from America, United Kingdom, Europe, and Australasia. Members were invited to complete a 13-item questionnaire regarding screening techniques, first-line and second-line therapies in endovascular intervention, and the role of angioplasty. Answers were compared using χ(2) testing for nonparametric data. RESULTS: Data from 344 respondents from 32 countries were analyzed: 167 non-United States and 177 U.S. RESPONDENTS: More than half of all clinicians had 10+ years of experience in units with a mixture of higher and lower case volumes. Daily transcranial Doppler ultrasonography was the most commonly used screening technique by both U.S. (70%) and non-U.S. (53%) practitioners. Verapamil was the most common first-line therapy in the United States, whereas nimodipine was most popular in non-U.S. countries. Angioplasty was performed by 83% of non-U.S. and 91% of U.S. clinicians in the treatment of vasospasm; however, more U.S. clinicians reported using angioplasty for distal vasospasm. CONCLUSIONS: Treatment practices for DCI vary considerably, with the greatest variability in the choice of agent for intra-arterial therapy. Our data demonstrate the wide variation of approaches in use at present. However, without further clinical trials and development of a uniform standard of best practice, variability in treatment and outcome for DCI is likely to continue.

Melatonin responsive hemicrania continua in which indomethacin was associated with contralateral headache.

Headache is a well-documented side effect of indomethacin in the older medical literature; however, it has rarely been commented on in indomethacin-responsive hemicrania continua. We describe the case of a 60-year-old woman with left-sided hemicrania continua whose indomethacin treatment was associated with a continuous right-sided migraine. Her indomethacin therapy was discontinued heralding a return of her left-sided hemicrania continua and a resolution of her right-sided migraine. Her hemicrania continua then responded well to melatonin, with recurrence on stopping and improvement on restarting. This is the most detailed description of headache as a side effect of indomethacin in a headache patient we are aware of, and one of only a few reported cases of melatonin-responsive hemicrania continua. We review the evidence of headache as a side effect of indomethacin in order to highlight its importance in the treatment of headache disorders. We emphasize that indomethacin headache response may be more than simply a beneficial or neutral one and might be relevant to some cases of apparently indomethacin-resistant hemicrania continua. We hope this case may encourage clinicians to inquire about headache as a potential side effect of indomethacin.