1. Ng WT, Tsang RKY, Beitler JJ, et al. Contemporary management of the neck in nasopharyngeal carcinoma. Head Neck 2021;43:1949–63. Available from: https://onlinelibrary.wiley.com/doi/10.1002/hed.26685
For patients who present with suspicious cervical lymphadenopathy, especially in the endemic regions where NPC is prevalent, initial examination may be endoscopic examination and biopsy of the NP, rather than fine-needle aspiration of the neck mass. Subsequent work up includes appropriate biopsy of the primary tumor and/or the node, physical examination with particular attention to cranial nerve function, plasma Epstein–Barr virus (EBV) DNA, CT scanning, MR, and FDG-PET. Radiotherapy with or without chemotherapy remains the primary modality of treatment, while surgery is reserved for persistent nodal disease or relapse.
With improvement in radiological diagnostic accuracy and better characterization of the natural history of NPC nodal spread, continual refinements have been suggested in the AJCC/UICC TNM staging system. Among the various nodal features, recent data suggest that nodal volume, ECE, nodal necrosis, and parotid node involvement carry adverse prognostic significance. Selective nodal irradiation according to individual nodal risk has been increasingly adopted, and early data based on this approach appear promising. Furthermore, gradient dose prescription using a lower dose elective nodal irradiation (ENI) to subclinical regions may serve a potentially useful strategy for dose de-escalation with the objective of reducing toxicity and improving quality of life. Amidst excellent nodal control with IMRT, salvage neck surgery remains the standard of care for patients who develop nodal failure, and continued research is required to define the extent of neck dissection and the role of adjuvant therapy after salvage neck surgery.
4 tables, 1 figure
2. Sabiq F, Huang K, Patel A, et al. Novel imaging classification system of nodal disease in human papillomavirus‐mediated oropharyngeal squamous cell carcinoma prognostic of patient outcomes. Head Neck 2021;43:1854–63. Available from: https://onlinelibrary.wiley.com/doi/10.1002/hed.26657
Matted nodes in human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPC) is an independent predictor of distant metastases and decreased overall survival. The authors aimed to classify imaging patterns of metastatic lymphadenopathy, analyze their classification system for reproducibility, and assess its prognostic value based on radiological characteristics for 216 patients with HPV-mediated OPC.
The following imaging features were considered positive for extranodal extension: irregular capsular contour with indistinct lymph node margins and adjacent fat stranding, indicative of infiltration of adjacent fat planes; or invasion of adjacent structures such as paravertebral or sternocleidomastoid muscles, jugular veins or carotid arteries, or parotid or submandibular glands.
When assessing a cluster of abutting lymph nodes, imaging features of ENE were established as either absent (aLN), in the intervening fat planes only (iENE), or in the surrounding fat planes (i.e. along the external non-abutting borders) with or without also in the intervening fat planes (sENE).
The presence of ≥3 abutting lymph nodes with imaging features of surrounding extranodal extension (ENE), one subtype of matted nodes, was associated with worse 5-year overall survival, overall recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival.
3 tables, 6 figures including very helpful schematic of what the authors mean by intervening extranodal extension and surrounding extranodal extension
3. Shahjouei S, Tsivgoulis G, Farahmand G, et al. SARS-CoV-2 and stroke characteristics. Stroke 2021;52:117–30. Available from: https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.032927
The authors (and there are a boatload of them) conducted a multinational observational study on features of consecutive acute ischemic stroke, intracranial hemorrhage, and cerebral venous or sinus thrombosis among severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) –infected patients. They also investigated the risk of large vessel occlusion, stroke severity as measured by the NIHS Scale, and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with acute ischemic stroke. They explored the neuroimaging findings, features of patients who were asymptomatic for SARS-CoV-2 infection at stroke onset, and the impact of geographic regions and countries’ health expenditure on outcomes.
Of 432 patients included, 323 (74.8%) had acute ischemic stroke, 91 (21.1%) intracranial hemorrhage, and 18 (4.2%) cerebral venous or sinus thrombosis. A total of 183 (42.4%) patients were women, 104 (24.1%) patients were <55 years of age, and 105 (24.4%) patients had no identifiable vascular risk factors. Among acute ischemic stroke patients, 44.5% (126 of 283 patients) had large vessel occlusion; 10% had small artery occlusion according to the TOAST criteria. They observed a lower median NIHSS and higher rate of mechanical thrombectomy (12.4% versus 2%) in countries with middle-to-high health expenditure when compared with countries with lower health expenditure. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144 (37.8%) were asymptomatic at the time of admission for SARS-CoV-2 infection.
In conclusion, the authors observed a considerably higher rate of LVOs and a much lower rate of small-vessel occlusion and lacunar infarction when compared with the prior population studies. They also observed a relatively high number of young stroke and a high number of asymptomatic SARS-CoV-2 patients at stroke onset. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.
4 tables, no figures
4. American Heart Association/American Stroke Association Stroke Council Leadership. Diagnosis and management of cerebral venous sinus thrombosis with vaccine-induced thrombotic thrombocytopenia. Stroke 2021;52:2478–82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33914590
Cerebral venous sinus thrombosis (CVST) is a rare manifestation of cerebrovascular disease. Recent reports from the Centers of Disease Control and the U.S. Food and Drug Administration identified six cases of CVST associated with thrombocytopenia in U.S. patients who had received the Ad26.COV2.S (Janssen) Coronavirus disease 2019 (COVID-19) vaccine. Similar thromboembolic events were reported in Europe following ChAdOx1 nCoV-19 (AstraZeneca) vaccination. Both the Janssen and AstraZeneca vaccines contain adenoviral vectors. In contrast, there have been no cases of CVST reported with thrombocytopenia following administration of 182 million mRNA SARS-Cov2 vaccines. While awaiting further information on the causal nature of the relationships of vaccines to CVST with thrombocytopenia, clinicians should be aware of the symptoms to facilitate recognition of potential cases of CVST in patients receiving these vaccinations. The goal of this report is to heighten awareness of the apparent association between adenovirus SARS-CoV2 vaccinations and CVST with vaccine-induced immune thrombotic thrombocytopenia (VITT) and suggest approaches to management.
Among the symptoms of the women who experienced CVST after receiving the Ad26.COV2.S (Janssen) adenovirus-based SARS-CoV-2 vaccine in the US, the most common symptom was headache. Symptom onset occurred 6-13 days after receipt of the vaccine. The age range was 18-48 years. Five of 6 patients presented with headache, one of whom also had vomiting and one lethargy. A sixth patient had back pain. Two had hemiparesis, one aphasia, one neglect, and one loss of consciousness. Two patients had abdominal pain due to portal vein thrombosis. Several of the cerebral sinuses were affected. Patients were treated with heparin (n=4), nonheparin anticoagulants (n=5), platelets (n=3), intravenous immunoglobulin (n=3). At least one patient died.
There is limited information about optimal treatment of CVST with vaccine-induced immune thrombotic thrombocytopenia, but recommendations follow those of heparin induced thrombocytopenia (HIT) given similarities in the two conditions. While there are no published data on efficacy in VITT, intravenous immunoglobulin 1 g/kg body weight daily for 2 days, has been recommended after laboratory testing for PF4 antibodies has been sent. No heparin products in any dose should be given. Some experts recommend administration of steroids.
2 tables
5. Liu APY, Li BK, Pfaff E, et al. Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study. Acta Neuropathol 2021;141:771–85. Available from: https://doi.org/10.1007/s00401-021-02284-5
Pineal parenchymal tumors are rare central nervous system (CNS) neoplasms that encompass a spectrum of entities with the varied histologic appearance and clinical phenotypes. Accounting for < 1% of all CNS tumors, these range from World Health Organization (WHO) Grade 1 pineocytomas, to WHO Grade 2–3 pineal parenchymal tumors of intermediate differentiation (PPTIDs), and Grade 4 pineoblastomas (PBs). While resection alone will typically suffice for treatment of pineocytoma, the optimal adjuvant therapy needed for patients with PPTIDs is unclear, and many patients with PB succumb to their disease despite intensive cytotoxic chemotherapy as well as craniospinal radiotherapy.
Recent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked the power to integrate molecular and clinical findings. The different proposed molecular group structures also highlighted a need to reach consensus on a robust and relevant classification system. The authors performed a meta-analysis on 221 patients with molecularly characterized pineoblastomas and pineal parenchymal tumors of intermediate differentiation. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical, and genomic features of patients and samples from these pineal tumor groups were annotated. Four clinically and biologically relevant consensus PB groups were defined: PB-miRNA1 (n = 96), PB-miRNA2 (n = 23), PB-MYC/FOXR2 (n = 34), and PB-RB1 (n = 25). A final molecularly distinct group, designated PPTID (n = 43), comprised histological PPTID and PBs.
While patients with PB-miRNA2 and PPTID had superior outcome (100% and 85% 5-year survival), survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 or PB-RB1 (20%). Reduced-dose CSI was adequate for patients with average-risk, PB-miRNA1/2 disease.
5 figures, 1 table, no imaging
6. Fujita K, Tanaka K, Yamagami H, et al. Outcomes of large vessel occlusion stroke in patients aged ≥90 years. Stroke 2021;52:1561–69. Available from: https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031386
Of 2420 acute ischemic stroke patients with large vessel occlusion in a prospective, multicenter, nationwide registry in Japan, patients aged ≥90 years with occlusion of the internal carotid artery or M1 segment of the middle cerebral artery were included. The primary effectiveness outcome was a favorable outcome at 3 months, defined as achieving a modified Rankin Scale score of 0 to 2 or return to at least the prestroke modified Rankin Scale score at 3 months. Safety outcomes included symptomatic intracranial hemorrhage within 72 hours after onset.
A total of 150 patients (median age, 92 years) were analyzed. EVT was performed in 49 patients (32.7%; mechanical thrombectomy, n=43). The EVT group showed shorter time from onset to hospital arrival, higher ASPECTS, and a higher rate of treatment with intravenous thrombolysis than the medical management group. The favorable outcome was seen in 28.6% of the EVT group and 6.9% of the medical management group. EVT was associated with the favorable outcome. Rates of symptomatic intracranial hemorrhage were similar between the EVT group (0.0%) and the medical management group.
In conclusion, patients aged ≥90 years who underwent EVT had shorter time from onset to hospital arrival, higher ASPECTS, a higher rate of treatment with IVT, and achieved better functional outcomes than those treated with medical management. Symptomatic ICH was not increased in the EVT group compared with the medical management group. Given proper patient selection, withholding EVT solely based on the age of patients may not offer the best chance of good outcome.
3 tables, 3 figures, no imaging
7. Hosp JA, Dressing A, Blazhenets G, et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain 2021;144:1263–76. Available from: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab009/6209743
In this prospective cohort study, the authors assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients were included in the cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance <26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with >2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and FDG PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients in the subacute stage of disease were included in the register.
Most frequently, gustation and olfaction were disturbed in 29/29 and 25/ 29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.
The present prospective register study highlights neocortical dysfunction as a neurological sequela of COVID-19 by identifying cognitive decline in COVID-19 inpatients at the subacute stage using comprehensive neuropsychological testing and functional imaging with 18FDG PET.
6 figures, 3 tables
8. Fares J, Ulasov I, Timashev P, et al. Emerging principles of brain immunology and immune checkpoint blockade in brain metastases. Brain 2021;144:1046–66. Available from: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab012/6248197
Generally, the brain boasts an immunosuppressive environment that does not permit the trafficking of immune cells. Discoveries in the past decade have shown that a special lymphatic system exists to drain from the dura mater of the brain to the peripheral lymph nodes. It has been further emphasized that endothelial, epithelial and glial brain barriers possess varied accessibility to different immune-cell subtypes. New evidence continues to reveal a role for immune cells in the tumor microenvironment. These results have debunked the widely held belief that the brain is an immune-privileged organ, which is free from immune activity. In fact, antigens derived from the brain can induce an immune reaction in cervical lymph nodes. In addition, this heterogeneous blood–tumor barrier permeability in the setting of brain metastasis can facilitate the infiltration of multiple immune cells from the peripheral circulation. As acumen on the immunology of brain metastases continues to grow, it has been learned that the CNS is home to a variety of antigen-presenting cells (APCs) such as microglia, dendritic cells and macrophages, as well as astrocytes. T cells are now known to roam freely in the brain. This does not take away from the uniqueness of the brain immune system, as it continues to be more limited than the immune system in peripheral organs.
Patients with brain metastases continue to be excluded from clinical trials due to their dismal outcomes and poor prognoses. Many prospective and retrospective immunotherapeutic studies exclude patients with brain metastases despite increasing data that point to potential efficacy against intracranial metastases. In a multivariate analysis, brain metastases were not associated with poorer survival in patients treated with immune checkpoint inhibitors in NSCLC. Stable patients with brain metastases without baseline corticosteroids and a good diagnosis-specific graded prognostic assessment (DS-GPA) classification have the best prognosis. Combining different immune checkpoint inhibitors together or with radiation, chemotherapy, targeted therapy, antiangiogenic therapy and/or neurosurgery seems to potentiate their effect in the setting of brain metastases. Therefore, randomized controlled trials for patients with brain metastases are needed to fully understand the exact clinical benefit of immunotherapy as monotherapy or in combination.
4 figures, 4 tables, no imaging
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