Nonaneurysmal perimesencephalic subarachnoid hemorrhage on noncontrast head CT: An accuracy, inter-rater, and intra-rater reliability study.

BACKGROUND AND PURPOSE: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. MATERIALS AND METHODS: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2-5. Reliability was estimated using Gwet's AC1 (κG), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer's V test. Multi-rater accuracy of NCCT in predicting negative CA was explored. RESULTS: Inter-rater reliability for the presence of NAPSAH was moderate (κG = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated (κG = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling (κG = 0.79) and extension to LSF (κG = 0.79). Mean intra-rater reliability was substantial (κG = 0.65). NAPSAH weakly correlated with CA decision (V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. CONCLUSION: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest.

Innate immunity activation in the early brain injury period following subarachnoid hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is a catastrophic disease with devastating consequences, including a high mortality rate and severe disabilities among survivors. Inflammation is induced following SAH, but the exact role and phenotype of innate immune cells remain poorly characterized. We investigated the inflammatory components of the early brain injury in an animal model and in SAH patients. METHOD: SAH was induced through injection of blood in the subarachnoid space of C57Bl/6 J wild-type mice. Prospective blood collections were obtained at 12 h, days 1, 2, and 7 to evaluate the systemic inflammatory consequences of SAH by flow cytometry and enzyme-linked immunosorbent-assay (ELISA). Brains were collected, enzymatically digested, or fixed to characterize infiltrating inflammatory cells and neuronal death using flow cytometry and immunofluorescence. Phenotypic evaluation was performed at day 7 using the holding time and footprint tests. We then compared the identified inflammatory proteins to the profiles obtained from the plasma of 13 human SAH patients. RESULTS: Following SAH, systemic IL-6 levels increased rapidly, whereas IL-10 levels were reduced. Neutrophils were increased both in the brain and in the blood reflecting local and peripheral inflammation following SAH. More intracerebral pro-inflammatory monocytes were found at early time points. Astrocyte and microglia activation were also increased, and mice had severe motor deficits, which were associated with an increase in the percentage of caspase-3-positive apoptotic neurons. Similarly, we found that IL-6 levels in patients were rapidly increased following SAH. ICAM-1, bFGF, IL-7, IL-12p40, and MCP-4 variations over time were different between SAH patients with good versus bad outcomes. Moreover, high levels of Flt-1 and VEGF at admission were associated with worse outcomes. CONCLUSION: SAH induces an early intracerebral infiltration and peripheral activation of innate immune cells. Furthermore, microglia and astrocytic activation are present at later time points. Our human and mouse data illustrate that SAH is a systemic inflammatory disease and that immune cells represent potential therapeutic targets to help this population of patients in need of new treatments.

Outcome of intracranial arterial stenting of symptomatic atherosclerotic disease: A single center experience from Saudi Arabia.

OBJECTIVE: To present our local experience with intracranial angioplasty and stenting used for the treatment of symptomatic intracranial stenosis to assess its safety, efficacy, and outcome. METHODS: This is a retrospective review of all the patients with symptomatic intracranial atherosclerotic disease who underwent endovascular treatment in King Faisal Specialist Hospital and research center, Jeddah, Kingdom of Saudi Arabia from January 2003 to December 2014. Clinical, procedural, and outcome variables were gathered. RESULTS: We identified 22 patients who were referred for stenting of symptomatic intracranial atherosclerotic stenosis. In all but 3, the stents were deployed successfully (86% procedural success rate). The procedure was carried out under conscious sedation in 32%. Excellent flow was restored immediately in all successfully-stented cases. Post procedural strokes occurred in 4 patients (17.4%). One non-neurological death was identified in a patient who suffered a major post procedural stroke (4.3%). CONCLUSION: Intracranial atherosclerotic disease is not uncommon in our population. Angioplasty and stenting might be a valid option for the treatment of patients with recurrent symptoms despite optimal medical treatment.

Severe Cerebral Vasospasm Caused by Acute on Top of Chronic Spontaneous Subdural Hematoma: A Case Report and Review of the Literature.

Cerebral vasospasm is a well-known phenomenon that has been associated with subarachnoid hemorrhage due to aneurysmal bleeding. It can lead to serious outcomes if not recognized and treated promptly. It happens most frequently following cases of aneurysmal subarachnoid hemorrhage. Other causes include traumatic brain injury, reversible cerebral vasoconstriction syndrome, post-tumor resection, and non-aneurysmal subarachnoid hemorrhage. We describe a case of severe clinical vasospasm following acute on top of chronic spontaneous subdural hematoma in a patient with corpus callosum agenesis. Also, a small literature review of the possible risk factors of such occurrence is discussed.

Outcomes of resective surgery in pediatric patients with drug-resistant epilepsy: A single-center study from the Eastern Mediterranean Region.

OBJECTIVE: Epilepsy surgery is widely accepted as an effective therapeutic option for carefully selected patients with drug-resistant epilepsy (DRE). There is limited data on the outcome of epilepsy surgery, especially in pediatric patients from the Eastern Mediterranean region. Hence, we performed a retrospective study examining the outcomes of resective surgery in 53 pediatric patients with focal DRE. METHODS: Patients with focal DRE who had undergone epilepsy surgery were included in the present study. All patients underwent a comprehensive presurgical evaluation. Postoperative seizure outcomes were classified using the Engel Epilepsy Surgery Outcome Scale. RESULTS: After surgery, 33 patients (62.2%) were Class I according to the Engel classification of surgical outcomes; eight patients (15.0%) were Class II, 11 (20.7%) were Class III, and one (1.8%) was Class IV. The relationships of presurgical, surgical, and postsurgical clinical variables to seizure outcomes were compared. Older age at seizure onset, older age at the time of surgery, the presence of focal to bilateral tonic-clonic seizures, seizure duration over 2 minutes, unsuccessful treatment with three or fewer antiseizure medications, lesions confined to one lobe (as demonstrated via magnetic resonance imaging [MRI]), surgical site in the temporal lobe, and histopathology including developmental tumors were significantly linked to an Engel Class I outcome. A univariate analysis of excellent surgical outcomes showed that lateralized semiology, localized interictal and ictal electroencephalogram (EEG) discharges, lateralized single-photon emission computed tomography and positron emission tomography findings, and temporal lobe resections were significantly related to excellent seizure outcomes. SIGNIFICANCE: The results of our study are encouraging and similar to those found in other centers around the world. Epilepsy surgery remains an underutilized treatment for children with DRE and should be offered early.

Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification.

The classification of central nervous system (CNS) glioma went through a sequence of developments, between 2006 and 2021, started with only histological approach then has been aided with a major emphasis on molecular signatures in the 4th and 5th editions of the World Health Organization (WHO). The recent reformation in the 5th edition of the WHO classification has focused more on the molecularly defined entities with better characterized natural histories as well as new tumor types and subtypes in the adult and pediatric populations. These new subclassified entities have been incorporated in the 5th edition after the continuous exploration of new genomic, epigenomic and transcriptomic discovery. Indeed, the current guidelines of 2021 WHO classification of CNS tumors and European Association of Neuro-Oncology (EANO) exploited the molecular signatures in the diagnostic approach of CNS gliomas. Our current review presents a practical diagnostic approach for diffuse CNS gliomas and circumscribed astrocytomas using histomolecular criteria adopted by the recent WHO classification. We also describe the treatment strategies for these tumors based on EANO guidelines.

Association Between CD204-Expressed Tumor-Associated Macrophages and MGMT-Promoter Methylation in the Microenvironment of Grade 4 Astrocytomas.

Background: Tumor-associated macrophages (TAMs) are principal immune cells in glioma microenvironment which support tumor growth and proliferation. Our aim in this study was to assess the relationship between CD204-expressed TAMs and O6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation in World Health Organization (WHO) grade 4 astrocytomas, and its impact on patient's clinical outcome. Methods: The expression of CD204 + TAMs was quantitively assessed on 45 samples of WHO grade 4 astrocytomas using immunohistochemistry. MGMT-promoter methylation was tested by methylation techniques. The relationship between TAMs, MGMT-promoter methylation, and recurrence-free interval (RFI) was statistically analyzed. Results: There were 10 cases (22.2%) with isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytoma and 35 cases (77.8%) with IDH-wildtype glioblastoma. MGMT-promotor was methylated in 18 cases (40%), unmethylated in 15 cases (33%), and the remaining 12 cases showed no MGMT status because of nucleic acid degradations. The expression of CD204+ TAMs was high in 32 cases (71.7%) and low in 13 cases (28.8%). The relationship between IDH1 mutation and CD204+ TAM expression was insignificant (P = 0.93). However, the significant difference was found between MGMT methylation and CD204+ TAMs expression (P = 0.01), in which CD204+ TAMs were diffusely expressed in MGMT-methylated cases. There was no significant difference in RFI between CD204+ TAMs expression, MGMT-promoter methylation and treatment modalities. Conclusions: Grade 4 astrocytomas with diffusely expressed CD204+ TAMs are usually associated with MGMT-promoter methylation. Although this association is unclear, CD204+ TAMs may neutralize the effect of MGMT-DNA protein to loss its function, which contributes to tumor progression. This relationship had no significant impact on the patient's clinical outcome after different treatment modalities.

The Diagnostic Value of Pan-Trk Expression to Detect Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion in CNS Tumours: A Study Using Next-Generation Sequencing Platform.

Background: Neurotrophic tyrosine receptor kinase (NTRK) fusion has been detected in rare types of CNS tumours, which can promote tumorigenesis. The efficacy of Trk inhibitor became a significant therapeutic interest. Our aim was to investigate whether Pan-Trk immunohistochemistry (IHC) is a reliable and efficient marker for detecting NTRK-fusion in different brain tumours. Methods: This study included 23 patients diagnosed with different types of CNS tumours. Testing for Pan-Trk IHC with monoclonal Ab (EPR17341) has been performed on all FFPE tissues. Parallelly, NTRK-rearrangements were tested using both DNA and RNA-based next-generation sequencing (NGS) assay using TruSight Onco500 platform. Results: The cohort included eight pilocytic astrocytomas, one oligodendroglioma, six IDHwildtype glioblastomas, four IDHmutant grade four astrocytomas, and one sample of each (astroblastoma, central neurocytoma, medulloblastoma, and liponeurocytoma). The mean age was 35 years; seven cases were in the paediatric age group, and 16 were adult. Pan-Trk expression was detected in 11 (47.8%) tumours, and 12 (52.1%) tumours showed no Pan-Trk expression. Nine Cases (82%) with different Pan-Trk expressions did not reveal NTRK-rearrangement. The other two positively expressed cases (liponeurocytoma and glioblastoma) were found to have NTRK2-fusions (SLC O 5A1-NTRK2, AGBL4-NTRK2, BEND5-NTRK2). All the 12 cases (100%) with no Pan-Trk expression have shown no NTRK-fusions. There was no statistically significant association between Pan-Trk expression and NTRK-fusion (p = 0.217). The detection of NTRK- fusions using NGS had high specificity over NTRK-fusion detection by using Pan-Trk IHC. Conclusion: Pan-Trk IHC is not a suitable tissue-efficient biomarker to screen for NTRK-fusions in CNS tumours, however RNA-based NGS sequencing should be used as an alternative method.

Cryptogenic cervical intramedullary abscess with rapidly progressive myelopathy: illustrative case.

BACKGROUND: The purpose of the present case report is to highlight the presentation, workup, clinical decision making, and operative intervention for a 68-year-old woman who developed rapidly progressive myelopathy secondary to idiopathic cervical intramedullary abscess. OBSERVATIONS: The patient underwent laminectomy and aspiration/biopsy of the lesion. Intraoperatively, division of the posterior median sulcus released a large volume of purulent material growing the oral pathogens Eikenella corrodens and Gemella morbillorum. Broad-spectrum antibiotics were initiated postoperatively. At the 6-month follow-up, the patient had almost completely recovered with some persistent hand dysesthesia. Complete infectious workup, including full dental assessment and an echocardiogram, failed to reveal the source of her infection. LESSONS: The authors report the first case of cryptogenic spinal intramedullary abscess secondary to Eikenella spp. and Gemella spp. coinfection. Intramedullary abscesses are exceptionally rare and most commonly develop in children with dermal sinus malformations or in the context of immunosuppression. In adults without risk factors, they can readily be mistaken for more common pathologies in this age group, such as intramedullary neoplasms or demyelinating disease. Prompt diagnosis and management based on rapidly progressive myelopathy, assessment of infectious risk factors and/or symptoms, and targeted imaging are critical to avoid potentially devastating neurological sequelae.

Implantable Pulse Generators for Deep Brain Stimulation: Challenges, Complications, and Strategies for Practicality and Longevity.

Deep brain stimulation (DBS) represents an important treatment modality for movement disorders and other circuitopathies. Despite their miniaturization and increasing sophistication, DBS systems share a common set of components of which the implantable pulse generator (IPG) is the core power supply and programmable element. Here we provide an overview of key hardware and software specifications of commercially available IPG systems such as rechargeability, MRI compatibility, electrode configuration, pulse delivery, IPG case architecture, and local field potential sensing. We present evidence-based approaches to mitigate hardware complications, of which infection represents the most important factor. Strategies correlating positively with decreased complications include antibiotic impregnation and co-administration and other surgical considerations during IPG implantation such as the use of tack-up sutures and smaller profile devices.Strategies aimed at maximizing battery longevity include patient-related elements such as reliability of IPG recharging or consistency of nightly device shutoff, and device-specific such as parameter delivery, choice of lead configuration, implantation location, and careful selection of electrode materials to minimize impedance mismatch. Finally, experimental DBS systems such as ultrasound, magnetoelectric nanoparticles, and near-infrared that use extracorporeal powered neuromodulation strategies are described as potential future directions for minimally invasive treatment.

A two-step approach for mining patient treatment pathways in administrative healthcare databases.

Clustering electronic medical records allows the discovery of information on healthcare practices. Entries in such medical records are usually composed of a succession of diagnostics or therapeutic steps. The corresponding processes are complex and heterogeneous since they depend on medical knowledge integrating clinical guidelines, the physician's individual experience, and patient data and conditions. To analyze such data, we are first proposing to cluster medical visits, consultations, and hospital stays into homogeneous groups, and then to construct higher-level patient treatment pathways over these different groups. These pathways are then also clustered to distill typical pathways, enabling interpretation of clusters by experts. This approach is evaluated on a real-world administrative database of elderly people in Québec suffering from heart failures.

Anterolateral Cervical Kyphoplasty for Metastatic Cervical Spine Lesions.

STUDY DESIGN: Retrospective case series. PURPOSE: To evaluate the clinical and radiological efficacy of anterolateral kyphoplasty for cervical spinal metastasis. OVERVIEW OF LITERATURE: Although the spine is the third most common site of tumor metastasis, the cervical spine is the least commonly affected (incidence, 10%-15%). Surgical decompression is highly challenging because of the proximity of neural and vascular elements. Kyphoplasty for cervical spine metastasis has been described in small case reports with promising results. METHODS: Retrospective analysis of a prospective collected single-center spine metastasis database was done for cervical kyphoplasty cases. Data pertaining to age, sex, primary tumor diagnosis, modified Tokuhashi score, Spinal Instability Neoplastic Score (SINS), preoperative Visual Analog Scale (VAS) score, and analgesic medication were extracted. Postoperative data included VAS score at postoperative day 1, duration of hospitalization, self-reported functional outcome, and VAS score at the last follow-up. RESULTS: Eleven patients (mean age, 62.5 years) with cervical spine metastases were treated with 15-level kyphoplasty. Mean Tokuhashi score was 8.1, and mean SINS was 7.85. Mean preoperative pain score was 7.1, and 82% of patients used opioid analgesics. Mean total bleeding volume was 100 mL. Mean complication-free length of stay was 2.6 days with a decrease in postoperative pain (VAS score=2.8, p <0.05). There was a 56% decrease in opioid dosage and the number of consumed analgesics (1.09, p =0.004). Eightytwo percent of the patients reported excellent improvement at the last follow-up self-assessment. CONCLUSIONS: To our knowledge, this case series represents the largest series of vertebral augmentation using balloon kyphoplasty for cervical spinal metastasis. This technique is associated with low postoperative complications as well as significant decrease in pain, use of opioids, and length of hospital stay. The main indications for vertebral kyphoplasty are lytic lesions of the cervical spine, painful lesions refractory to medical treatment, SINS score of 6-10, and absence of posterior wall defect.

Endovascular suction thrombectomy for severe cerebral venous sinus thrombosis: A report of two cases.

Cerebral venous sinus thrombosis (CVST) is a severe clinical condition that manifests with diverse symptoms that can be mild, taking the form of a headache, or can be life-threatening, with raised intracranial pressure and herniation. Despite systemic anticoagulation treatment, CVST still carries a mortality risk of approximately 10% because of the failure of venous recanalization by anticoagulants alone. This paper describes two cases with extensive CVST who presented with progressive neurological deterioration despite adequate systemic anticoagulation treatment. Both patients were successfully treated with endovascular clot removal using suction thrombectomy techniques with immediate recanalization of the sinuses and rapid radiographic improvement. The described therapy appears effective and safe; however, further studies are needed to validate the effectiveness of this treatment.

Bedside transcranial sonography monitoring in a patient with hydrocephalus post subarachnoid hemorrhage.

BACKGROUND: Development of hydrocephalus can occur after subarachnoid hemorrhage (SAH). Typically, it is diagnosed with computed tomography, CT, scan. However, transcranial sonography (TCS) can be used particularly in patients with craniotomy which removes the acoustic interference of the skull and allows a closer up visualization of brain structures through the skin. CASE PRESENTATION: We report a 73-year-old woman who was hospitalized for SAH and developed acute hydrocephalus requiring an external ventricular drain (EVD). In this patient, detection and monitoring of hydrocephalus was done and monitored with a small pocket-sized TCS device. Nine days after surgery, weaning of the EVD was attempted. Prior to EVD closure and removal, TCS showed a measurement of the 3rd ventricle at around 1.16 cm. On the third day, the patient deteriorated clinically and the TCS showed a dilated 3rd ventricle measuring 1.37 cm which correlated well with computed tomography and with clinical signs of active hydrocephalus as both her sensorium and communication were affected. Subsequently following EVD re-installation, on the next day, TCS showed that the 3rd ventricle dimension was reduced to 0.99 cm and the following day it went down to 0.69 cm. CONCLUSIONS: Patients with SAH and in particular those with a craniotomy can be monitored easily at the bedside with hand-held TCS for the development and monitoring of hydrocephalus.