The Molecular Landscape of Primary CNS Lymphomas (PCNSLs) in Children and Young Adults.

Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 months and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older (p = 0.029). CDKN2A HD was associated with a shorter OS (p < 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.

Task-based EEG and fMRI paradigms in a multimodal clinical diagnostic framework for disorders of consciousness.

Disorders of consciousness (DoC) are generally diagnosed by clinical assessment, which is a predominantly motor-driven process and accounts for up to 40 % of non-communication being misdiagnosed as unresponsive wakefulness syndrome (UWS) (previously known as prolonged/persistent vegetative state). Given the consequences of misdiagnosis, a more reliable and objective multimodal protocol to diagnosing DoC is needed, but has not been produced due to concerns regarding their interpretation and reliability. Of the techniques commonly used to detect consciousness in DoC, task-based paradigms (active paradigms) produce the most unequivocal result when findings are positive. It is well-established that command following (CF) reliably reflects preserved consciousness. Task-based electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can detect motor-independent CF and reveal preserved covert consciousness in up to 14 % of UWS patients. Accordingly, to improve the diagnostic accuracy of DoC, we propose a practical multimodal clinical decision framework centered on task-based EEG and fMRI, and complemented by measures like transcranial magnetic stimulation (TMS-EEG).

Machine learning-based prediction of COVID-19 mortality using immunological and metabolic biomarkers.

COVID-19 mortality prediction Background COVID-19 has become a major global public health problem, despite prevention and efforts. The daily number of COVID-19 cases rapidly increases, and the time and financial costs associated with testing procedure are burdensome. Method To overcome this, we aim to identify immunological and metabolic biomarkers to predict COVID-19 mortality using a machine learning model. We included inpatients from Hong Kong's public hospitals between January 1, and September 30, 2020, who were diagnosed with COVID-19 using RT-PCR. We developed three machine learning models to predict the mortality of COVID-19 patients based on data in their electronic medical records. We performed statistical analysis to compare the trained machine learning models which are Deep Neural Networks (DNN), Random Forest Classifier (RF) and Support Vector Machine (SVM) using data from a cohort of 5,059 patients (median age = 46 years; 49.3% male) who had tested positive for COVID-19 based on electronic health records and data from 532,427 patients as controls. Result We identified top 20 immunological and metabolic biomarkers that can accurately predict the risk of mortality from COVID-19 with ROC-AUC of 0.98 (95% CI 0.96-0.98). Of the three models used, our result demonstrate that the random forest (RF) model achieved the most accurate prediction of mortality among COVID-19 patients with age, glomerular filtration, albumin, urea, procalcitonin, c-reactive protein, oxygen, bicarbonate, carbon dioxide, ferritin, glucose, erythrocytes, creatinine, lymphocytes, PH of blood and leukocytes among the most important biomarkers identified. A cohort from Kwong Wah Hospital (131 patients) was used for model validation with ROC-AUC of 0.90 (95% CI 0.84-0.92). Conclusion We recommend physicians closely monitor hematological, coagulation, cardiac, hepatic, renal and inflammatory factors for potential progression to severe conditions among COVID-19 patients. To the best of our knowledge, no previous research has identified important immunological and metabolic biomarkers to the extent demonstrated in our study. Supplementary Information: The online version contains supplementary material available at 10.1186/s44247-022-00001-0.

A Mendelian randomization-based exploration of red blood cell distribution width and mean corpuscular volume with risk of hemorrhagic strokes.

Red blood cell distribution width (RCDW) and mean corpuscular volume (MCV) are associated with different risk factors for hemorrhagic stroke. However, whether RCDW and MCV are causally related to hemorrhagic stroke remains poorly understood. Therefore, we explored the causality between RCDW/MCV and nontraumatic hemorrhagic strokes using Mendelian randomization (MR) methods. We extracted exposure and outcome summary statistics from the UK Biobank and FinnGen. We evaluated the causality of RCDW/MCV on four outcomes (subarachnoid hemorrhage [SAH], intracerebral hemorrhage [ICH], nontraumatic intracranial hemorrhage [nITH], and a combination of SAH, cerebral aneurysm, and aneurysm operations) using univariable MR (UMR) and multivariable MR (MVMR). We further performed colocalization and mediation analyses. UMR and MVMR revealed that higher genetically predicted MCV is protective of ICH (UMR: odds ratio [OR] = 0.89 [0.8-0.99], p = 0.036; MVMR: OR = 0.87 [0.78-0.98], p = 0.021) and nITH (UMR: OR = 0.89 [0.82-0.97], p = 0.005; MVMR: OR = 0.88 [0.8-0.96], p = 0.004). There were no strong causal associations between RCDW/MCV and any other outcome. Colocalization analysis revealed a shared causal variant between MCV and ICH; it was not reported to be associated with ICH. Proportion mediated via diastolic blood pressure was 3.1% (0.1%,14.3%) in ICH and 3.4% (0.2%,15.8%) in nITH. The study constitutes the first MR analysis on whether genetically elevated RCDW and MCV affect the risk of hemorrhagic strokes. UMR, MVMR, and mediation analysis revealed that MCV is a protective factor for ICH and nITH, which may inform new insights into the treatments for hemorrhagic strokes.

Dose-Response Relationship and Threshold Drug Dosage Identification for a Novel Hybrid Mechanical-Thrombolytic System with an Ultra-Low Dose Patch.

INTRODUCTION: Ischemic stroke treatment has advanced in the last two decades and intravenous thrombolysis is now considered the standard of care for selected patients. Recanalization can also be achieved by mechanical endovascular treatment for patients with large vessel occlusions. Complicating treatment-related symptomatic intracerebral hemorrhage and prolonged needle-to-recanalization times have been identified as major determinants of poor three-month functional outcomes. A hybrid mechanical-thrombolytic system with a patch imbued with an ultra-low dose of thrombolytic agents loaded onto a stent-retriever has been developed. METHODS: In this study, the in situ dose-response relationship of the thrombolytic patch imbued with up to 1000 IU of urokinase plasminogen activator (uPA) was quantified using Raman spectroscopy. RESULTS: Thrombi of up to 400 µm thickness dissolved within 15 min when patches imbued with < 1% of the conventional thrombolysis therapy dosage were applied. The results demonstrated that low-dose thrombolytic patches can dissolve normal clots compressed in the blood vessel in a short time. 500 IU is the threshold uPA dosage in the thrombolytic patch that most effectively dissolves the clots. CONCLUSION: This study suggests that a novel endovascular stent-retriever loaded with an ultra-low drug dose fibrinolytic patch may be a suitable treatment for patients who are ineligible for conventional thrombolytic therapy.

"When the Benign Bleed" Vestibular Schwannomas with Clinically Significant Intratumoral Hemorrhage: A Case Series and Review of the Literature.

Vestibular schwannomas (VSs) are slow-growing benign neoplasms commonly located at the cerebellopontine angle. Although clinically significant hemorrhagic VSs are rarely encountered with only 75 patients previously reported, they could be life threatening. We discuss the presentation and outcomes of three patients with hemorrhagic VS as well as review the literature for this phenomenon. Consecutive adult patients with a histologically proven diagnosis of VS over a 9-year period were retrospectively reviewed. Fifty adult patients were identified with three (6%) having clinically significant intratumoral hemorrhage. This was defined as patients having acute to subacute symptoms with frank radiological evidence of hemorrhage. The mean age of diagnosis was 62 ± 9 years and the male-to female ratio was 2:1. The mean duration of symptoms, namely headache, vertigo, and sensorineural hearing impairment, was 26 ± 4 days with one patient presenting with acute coma. Retrosigmoid craniotomy for tumor resection was performed for all patients. Histopathological examination revealed extensive areas of microhemorrhage with considerable macrophage infiltration. All three patients were discharged with no additional neurological deficit and good functional performance. Clinically significant hemorrhagic VSs are rare, and patients may present with acute to subacute (i.e., within a month) symptoms of hearing loss headache, facial, or trigeminal nerve palsy. Macrophage infiltration is frequently encountered in tumor specimens and reflects the pivotal role of chronic inflammation in their pathophysiology. Surgical resection can lead to good outcomes with timely intervention.

Neurocognitive recovery and global cerebral perfusion improvement after cranioplasty in chronic sinking skin flap syndrome of 18 years: Case report using arterial spin labelling magnetic resonance perfusion imaging.

Sinking skin flap syndrome (SSFS) is a complication among long-term survivors of stroke or traumatic brain injury treated by decompressive craniectomy. The syndrome encompasses a wide spectrum of neurological symptoms including cognitive decline, seizures, speech and sensorimotor deficits. Early cranioplasty appears to improve cerebral perfusion, but the efficacy of cranioplasty in neurocognitive outcome in long-standing SSFS patient is unclear. We report a 64-year-old patient who suffered from traumatic brain injury and underwent decompressive craniectomy 18 years ago. She had chronic SSFS with pre-cranioplasty assessments demonstrating severe neurocognitive impairments which were static over time. After cranioplasty with custom-made polyetheretherketone flap to restore the 264 cm2 skull defect, magnetic resonance perfusion scan with pseudo-continuous arterial spin labelling technique showed a two-fold augmentation of cerebral blood flow in both frontal lobes, as well as areas distal to the sunken skin flap compared to baseline. This is accompanied by improvement of neurocognitive function as assessed by Montreal Cognitive Assessment, Neurobehavioral Cognitive State Examination, and Rivermead Behavioural Memory Test three and six months after cranioplasty. The patient's quality of life and that of her primary carer also showed improvement. This report describes a case of neurocognitive and global cerebral perfusion improvement after cranioplasty in the setting of prolonged SFSS of 18 years, and adds to the growing body of literature supporting the therapeutic role of cranioplasty beyond purely protective or cosmetic indications. The advantages and clinical utility of pCASL MR perfusion in assessing serial CBF before and after cranioplasty is illustrated.

A Giant Tumefactive Perivascular Space: A Rare Cause of Obstructive Hydrocephalus and Monoparesis.

Cerebral perivascular spaces (PVSs), otherwise known as Virchow-Robin spaces, are interstitial fluid-filled channels, <2 mm in diameter that form around arterial perforators as they course from the cortex into the brain parenchyma. In contrast, a giant tumefactive PVS is a rare entity comprising of clusters of such channels larger than 15mm resembling a neoplastic process as the name suggests. We report a 55-year-old male who presented with unsteady gait, cognitive decline, and left lower limb weakness for 6 months. Magnetic resonance imaging revealed a noncontrast enhancing multicystic intraaxial lesion of the right mesencephalon-diencephalon junction extending into the anterior third ventricle causing obstructive hydrocephalus. A ventriculoperitoneal shunt was inserted with a complete reversal of his neurological symptoms. Such PVSs can easily be misidentified for a cystic tumor, and their unique radiological features are discussed to prevent unnecessary surgery. We also demonstrate that when they cause hydrocephalus and midbrain compression symptoms cerebrospinal fluid shunting alone can result in excellent outcomes.

Progressive hemiparesis in a young man: Hemicerebral atrophy as the initial manifestation of basal ganglia germinoma.

Basal ganglia germinomas are rare and patients are classically young Oriental males presenting with gradually progressive hemiparesis. Although early treatment with chemo-radiotherapy can be curative and significantly improve the quality of life, medical attention is often delayed. A young Chinese male experienced a 6-month history of right hemiparesis with magnetic resonance imaging findings of hemicerebral atrophy and lentiform nucleus microhemorrhage, highly suggestive and early signs of basal ganglia germinomas. No further imaging was performed until 2 years later when he was admitted for acute neurological deterioration and a repeat scan revealed a large infiltrative tumor pathologically confirmed to be a pure germinoma.

Use of subdural drain for chronic subdural haematoma? A 4-year multi-centre observational study of 302 cases.

Chronic subdural haematoma (CSDH) is a common neurosurgical condition and is more prevalent in the ageing population. Studies have suggested that placement of subdural drains after burr-hole drainage was associated with lower recurrence rates. However, a considerable proportion of surgeons remained unconvinced of the effectiveness of drain placement and concerns exist with the potential complications this additional manoeuvre entails such as infection or bleeding. The aim of the present study is to evaluate the impact of subdural drain on CSDH recurrence and its safety. This is a multicentre observational study. Data of consecutive patients with burr-hole drainage performed for CSDH in three hospitals in Hong Kong during a four-year period from January 2008 to December 2011 were prospectively collected and retrospectively analysed. The primary outcome was symptomatic recurrence requiring re-operation. Secondary outcomes included the modified Rankin scales (mRS), morbidity and mortality at six months. A total of 302 patients were identified. The recurrence rate was 8.72% (13/149) with drain placement versus 16.3% (25/153) with no drain (Odds Ratio=0.489, 95%CI 0.240-0.998; p=0.0463). Local wound infection, subdural empyema, acute subdural haematoma and other complications had no significant difference. Six-month mRS, 30-day mortality and six-month mortality were comparable in both groups. In conclusion, the use of subdural drain significantly reduced recurrence with no significant increase in complications.

Risk factors for seizures and antiepileptic drug-associated adverse effects in high-grade glioma patients: A multicentre, retrospective study in Hong Kong.

AIM: The aim of this present study was to determine the frequency, as well as risk factors, for seizures and antiepileptic drug (AED)-associated adverse effects among high-grade glioma (HGG) patients. PATIENTS AND METHODS: A multicentre, retrospective study of adult Chinese Hong Kong patients from three neurosurgical centres diagnosed with supratentorial HGG between 1 January 2001 and 31 December 2010 was performed. RESULTS: A total of 198 patients, with a mean age of 55 years (range: 18-88) and a mean follow up of 15 months, was recruited. Most suffered from glioblastoma multiforme (GBM) (63 per cent) followed by anaplastic astrocytoma (25 per cent). Median overall survival for patients with GBM was 8 months, and 11 months for those with grade III gliomas. Prophylactic AED was prescribed in 165 patients (83 per cent), and 64 per cent of patients were continued until end of life or last follow up. A total of 112 patients (57 per cent) experienced seizures at a mean duration of 8 months postoperatively (range: 1 day-75 months). Independent predictors for seizures were a diagnosis of GBM [adjusted odds ratio (OR): 2.33, 95 per cent confidence interval (CI): 1.21-4.52] and adjuvant radiotherapy (adjusted OR: 2.97, 95 per cent CI: 1.49-6.62). One-fifth of patients (21 per cent) experienced AED adverse effects, with idiosyncratic cutaneous reactions and hepatotoxicity most frequently observed. An independent predictor for adverse effects was exposure to aromatic AED, such as phenytoin, carbamazepine and phenobarbital (adjusted OR: 3.32, 95 per cent CI: 1.32-8.40). CONCLUSIONS: Antiepileptic drug prescription for primary seizure prophylaxis is both pervasive and prolonged for HGG patients. Seizures occur frequently, but most were delayed and none were life threatening. Judicious prescription of AED is required, especially when a significant proportion of patients experience adverse effects. Patients with a diagnosis of GBM and exposure to radiotherapy are at risk. We suggest, contrary to present practice, that primary seizure prophylaxis be given only during the perioperative period and resumed when they occur. We also recommend avoidance of aromatic AED due to their association with idiosyncratic adverse effects.

Seropositive Neuromyelitis Optica imitating an Intramedullary Cervical Spinal Cord Tumor: Case Report and Brief Review of the Literature.

A 44-year-old woman with progressive cervical myelopathy and central cord syndrome was noted to have an extensive cervical intramedullary contrast-enhancing lesion on magnetic resonance imaging (MRI). The lesion resembled a spinal astrocytoma or ependymoma that required surgical intervention. She was subsequently diagnosed to have neuromyelitis optica (NMO), a rare idiopathic inflammatory demyelinating disorder, when the clinical examination revealed left optic atrophy. This was confirmed by a test showing seropositivity for NMO-immunoglobulin (IgG). Disease control was achieved with corticosteroids and immunosuppressive therapy. We report a rare case of a patient with NMO who had MRI features that could have easily led to the condition being misdiagnosed as a spinal cord tumor. The importance of careful history taking, awareness of typical radiological findings and the usefulness of serum NMO-IgG as a diagnostic tool are emphasized.

Thrombosed large distal posterior inferior cerebellar artery aneurysm mimicking an infratentorial ependymoma.

Large or giant intracranial aneurysms can simulate brain tumors clinically and radiologically by virtue of their progressive mass effect. Unlike aneurysms from alternative locations, those arising from the distal posterior inferior cerebellar artery (PICA) are uncommon. We report a patient who experienced progressive hemiparesis with magnetic resonance imaging findings suggestive of an infratentorial ependymoma. Intraoperatively, a thrombosed large aneurysm of the distal PICA was unexpectedly encountered. The aneurysm was clipped and the patient did not develop any permanent neurological deficit. This case illustrates the radiological nuances of large aneurysms and infratentorial ependymomas. Three-dimensional contrast-enhanced magnetic resonance angiography can be falsely negative and the importance of the "target" sign is emphasized. One should be cognizant of this possible diagnosis for patients with midline fourth ventricular lesions in order to reduce surgical risk.

A 45-year-old woman with reversible bilateral hearing loss.

A 45-year-old woman complained of a progressive 2-month history of bilateral hearing impairment and diplopia on upward gaze. She had a history of a recurrent pineal region ganglioglioma with repeated tumor excision, adjuvant radiotherapy, and a ventriculo-peritoneal shunt performed 12 years prior. Subsequent imaging studies 6 years ago showed a pineal region cyst with progressive increase in size and a Rickham reservoir (Codman; Johnson & Johnson, Raynham, MA) was placed for percutaneous cyst fluid aspiration. The size of the cystic lesion remained static upon follow-up CT scans for several years.