1. Hagiwara Y, Koto M, Bhattacharyya T, et al. Long-term outcomes and toxicities of carbon-ion radiotherapy in malignant tumors of the sphenoid sinus. Head Neck. 2019;(July 2019):50-58. doi:10.1002/hed.25965
Carbon ion offers potentially superior dose distributions which allows to escalate the dose with the improved potential to spare the critical organs at risk (OAR). It also has higher linear energy transfer and increased relative biological effectiveness (RBE) leading to a possibility of increased tumor cell killing as compared to other radiation modalities such as photons or protons. Considering the radio-resistance of non-SCCs of sphenoid sinus and the close proximity of the target volume to critical structures, carbon-ion radiotherapy (C-ion RT) seems to be a promising curable option for many inoperable primary non-SCCs owing to its unique physical dose distribution and enhanced biological effectiveness.
This is a retrospective analysis of 22 patients of primary sphenoid carcinomas treated with definitive C-ion RT (inoperable or refused surgery). Adenoid cystic carcinoma was the most common histology (15 patients, 68.2%). The prescribed dose was 52.8 Gy (RBE) or 64 Gy (RBE) in 16 fractions over 4 weeks. The median follow-up of this cohort was 48.5 months. The actuarial local control and overall survival at 5 years were 51.0% and 62.7%, respectively. C-ion RT can provide a reasonably good clinical outcome in locally advanced sphenoid sinus malignancies with a marginally higher late toxicity profile because of extremely close proximity of the target volume to critical structures.
4 tables, 2 figures…1 with imaging
2. Wewel JT, Brahimaj BC, Kasliwal MK, Traynelis VC. Perioperative complications with multilevel anterior and posterior cervical decompression and fusion. J Neurosurg Spine. 2019;32(January):1-6. doi:10.3171/2019.6.spine198
In select patients, both anterior and posterior decompression are required to decompress the spinal cord. There is the need for staged or single-surgery anterior and posterior decompression and fusion in a subgroup of patients with CSM. However, few data have been published regarding perioperative morbidity associated with these complex operations. To date, the largest patient cohorts in which perioperative complications of anterior-posterior cervical fusions have been investigated in three series with 29, 30, and 35 patients.
A retrospective analysis was performed to identify intended single-stage anterior-posterior or posterior- anterior-posterior cervical spine decompression and fusion surgeries performed by the primary surgeon at Rush University Medical Center between 2009 and 2016. Cases in which true anterior-posterior cervical decompression and fusion was not performed (i.e., those involving anterior-only, posterior-only, or delayed circumferential fusion) were excluded from analysis. Data including standard patient demographic information, comorbidities, previous surgeries, and intraoperative course, along with postoperative outcomes and complications, were collected and analyzed. Perioperative morbidity was recorded during the 90 days following surgery.
Anterior procedures consisted of a minimum of 3-level and maximum of 6-level discectomies and instrumentation. All patients undergoing discectomy received a Cornerstone allograft (Medtronic). Anterior corpectomies spanned 1 to 3 levels. In the cases for which a corpectomy was required, either fibular allografts or stackable cages were utilized (Medtronic). Posterior fixation techniques were tailored to the patient and included occipital plating and C2 (pars, pedicle, or laminar), lateral mass, and pedicle screw fixation.
Seventy-two patients (29 male and 43 female, mean age 57.6 years) were included in the study. Fourteen patients (19.4%) were active smokers, and 56.9% had hypertension, the most common comorbidity. The most common clinical presentation was neck pain in 57 patients (79.2%). Twenty-three patients (31.9%) had myelopathy, and 32 patients (44.4%) had undergone prior cervical spine surgery. Average blood loss was 613 ml. Injury to the vertebral artery was encountered in 1 patient (1.4%). Recurrent laryngeal nerve palsy was observed in 2 patients (2.8%). Two patients (2.8%) had transient unilateral hand grip weakness. There were no permanent neurological deficits. Dysphagia was encountered in 45 patients (62.5%) postoperatively, with 23 (32%) requiring nasogastric parenteral nutrition and 9 (12.5%) patients ultimately undergoing percutaneous endoscopic gastrostomy (PEG) placement. Nine of the 72 patients required a tracheostomy (12%). The incidence of pneumonia was 6.9% (5 patients) overall, and 2 of these patients were in the tracheostomy group. Superficial wound infections occurred in 4 patients (5.6%). Perioperative death occurred in 1 patient. Reoperation was necessary in 10 patients (13.9%). Major perioperative complications (permanent neurological deficit, vascular injury, tracheostomy, PEG tube, stroke, or death) occurred in 30.6% of patients.
Single-session anterior-posterior cervical decompression and fusion is an inherently morbid operation required in select patients with cervical spondylotic myelopathy. In this large single-surgeon series, there was a major perioperative complication risk of 30.6% and minor perioperative complication risk of 80.6%.
1 figure, 3 tables ….figures include plain films
3. Zhao Q, Cheng L, Yan H, et al. The Anatomical Study and Clinical Significance of the Sinuvertebral Nerves at the Lumbar Levels. Spine (Phila Pa 1976). 2019;45(2):61-66. doi:10.1097/BRS.0000000000003190
SVNs are formed by somatic roots from the ventral ramus and by autonomic roots from the gray ramus communicans of the lumbar levels. In 1850, Luschka first described the SVN and proposed that this nerve was related to low-back pain based on its anatomical features. Many researchers have found that the SVN mainly receives and transmits mechanical or chemical stimulation from the intervertebral disc, the dorsal longitudinal ligament, and the ventral part of the dura mater.
One hundred lumbar intervertebral foramina from 10 cadavers were studied, and the existence and types of the sinuvertebral nerves in the lumbar intervertebral foramina were described. Detailed anatomic studies of the sinuvertebral nerves in the lumbar intervertebral foramina were performed. The sinuvertebral nerves could be divided into the following two types: Type I, SVN deputy branches, which directly enter the posterior lateral edge of the intervertebral disc and part of the vertebral body without entering the inside of the spinal canal; and Type II, SVN main trunks, which originate from the anterior surface of the spinal ganglia or the starting point of the gray ramus communicans of the nerve root in the IVF and insert into the spinal canal accompanied by the postcentral branch.
1 table, 5 figures with photos. Figures 4 and 5 most interesting to me, and easiest to figure out the orientation of the specimen.
4. Mattox AK, Yan H, Bettegowda C. The potential of cerebrospinal fluid–based liquid biopsy approaches in CNS tumors. Neuro Oncol. 2019;21(August):1509-1518. doi:10.1093/neuonc/noz156
Cancer is fundamentally a genetic disease. Research over the past two decades has shown that roughly 200 genes, when mutated, can drive tumor formation. A typical tumor contains 2 to 8 of these “driver gene” mutations, along with a range of “passenger” mutations that confer no selective advantage. Depending on the tumor type, a given cancer may have between 8 and 200 or more passenger mutations. The advent of massively parallel NGS and the accompanying bioinformatic tools allows for hundreds of millions of DNA strands to be sequenced simultaneously at high coverage. Targeted sequencing libraries may be prepared using PCR primers that amplify loci around common oncogene (eg, KRAS, BRAF, β-catenin) and tumor suppressor (eg, TP53, APC, Rb) mutations. Alternatively, whole genome sequencing libraries may be prepared and subsequently diluted to assess for mutations, enriched for specific genomic loci, or simply sequenced. Regardless of the technology used to prepare sequencing libraries, the overall goal is the same: detection of rare mutations found in circulating free (cf) DNA.
CSF may be the best hope for minimally invasive diagnosis and treatment monitoring of central nervous system (CNS) malignancies. Discovery/validation of cell-free nucleic acid and protein biomarkers has the potential to revolutionize CNS cancer care, paving the way for presurgical evaluation, earlier detection of recurrence, and the selection of targeted therapies. While detection of mutations, changes in RNA and miRNA expression, epigenetic alterations, and elevations of protein levels have been detected in the CSF of patients with CNS tumors, most of these biomarkers remain unvalidated. In this review, the authors focus on the molecular changes that have been identified in a variety of CNS tumors and profile the approaches used to detect these alterations in clinical samples. They further emphasize the importance of systemic collection of CSF and the establishment of standardized collection protocols.
The largest study to date includes 85 patients who underwent lumbar puncture postsurgery, radiation, and at least one systemic chemotherapy because they showed neurological signs or symptoms of progression. Using a NGS approach, Miller et al identified one or more mutations in cfDNA in the CSF of 49.4% of patients. Radiographic findings, including tumor progression, tumor burden, and spread of tumor towards the ventricular system or subarachnoid space were associated with higher levels of mutation. Importantly, Miller et al found that tumor evolution could be tracked through sequential biopsies of CSF. As the time between initial CSF draw and subsequent CSF collection increased, a greater diversity of mutations was observed, especially in those genes that code for growth factor signaling pathways. For example, in a patient with initial EGFR amplification and an EGFR missense mutation, subsequent CSF sampling showed amplification and mutation of platelet-derived growth factor receptor alpha (PDGFRA) and no alterations of EGFR. These findings mirror studies of sequential tumor biopsies in patients with glioma that show only 33–73% concordance of mutations over time.
2 figures, 1 table
5. Raychev R, Saver JL, Jahan R, et al. The impact of general anesthesia, baseline ASPECTS, time to treatment, and IV tPA on intracranial hemorrhage after neurothrombectomy: pooled analysis of the SWIFT PRIME, SWIFT, and STAR trials. J Neurointerv Surg. 2020;12(1):2-6. doi:10.1136/neurintsurg-2019-014898
Pooled individual patient-level data from three large prospective multicenter studies were analyzed for the incidence of different ICH subtypes, including any ICH, hemorrhagic transformation (HT), parenchymal hematoma (PH), subarachnoid hemorrhage (SAH), and symptomatic intracranial hemorrhage (sICH). All patients (n=389) treated with the Solitaire device were included in the analysis.
General anesthesia and higher baseline ASPECTS were associated with a lower probability of any ICH and hemorrhagic transformation. Longer time from onset to treatment was associated with a higher likelihood of HT and PH. Intravenous tissue plasminogen activator (IV-tPA) was also a strong predictor of PH.
The strong association of baseline ASPECTS with any ICH and HT in this study reaffirms these previous data and further establishes the ischemic volume as one of the most important factors influencing hemorrhage after reperfusion.
The authors note that this study is the first to report an inverse association between general anesthesia and the occurrence of ICH in the setting of neurothrombectomy. Although GA did not impact the most severe hemorrhage subtypes (sICH and PH), these findings provide signals about its protective effect against hemorrhage that warrant further exploration. While no definitive explanation regarding the relationship between GA and ICH can be drawn from this data. General anesthesia and smaller baseline ischemic core are associated with a lower probability of HT whereas IV-tPA and prolonged time to treatment increase the risk of PH after neurothrombectomy.
4 tables
6. Schmahmann JD, Guell X, Stoodley CJ, Halko MA. The Theory and Neuroscience of Cerebellar Cognition. Annu Rev Neurosci. 2019;42(1):337-364. doi:10.1146/annurev-neuro-070918-050258
The cerebellum had been thought for almost 200 years to be devoted exclusively to motor control. This may now be regarded as a quirk of history, resulting from a focus on obvious motor deficits while neglecting cognitive or neuropsychiatric phenomena that did not conform to established dogma. Vincenzo Malacarne (1776), who wrote the first treatise on the cerebellum and named many of its structures, studied the cerebellum to explore the relationship between the number of its folia and intelligence. We now know that the cerebellum is engaged in almost all neurological functions, i.e., sensorimotor, vestibular, cognitive, emotional-social-psychological, and autonomic, and that lesions of its different parts affect each of these domains.
This review commences with a consideration of a theoretical approach to the role of the cerebellum in the nervous system. It then discusses anatomical circuits defined in tract-tracing experiments, insights derived from functional imaging studies in humans, clinical syndromes, and therapeutic implications of this paradigm shift in understanding the cerebellum and its disorders.
Summary points:
- The cerebellum modulates cognition and emotion in the same way that it modulates motor control.
- Task-based and resting-state fMRI in humans demonstrate the previously identified double motor representation in the cerebellar anterior lobe (and adjacent region of lobule VI) and lobule VIII and a new triple nonmotor representation in the cerebellar posterior lobe in lobules VI/Crus I, Crus II/VIIB, and IX/X.
- The clinical neurology and neuropsychiatry of the cerebellum, including the description of cerebellar cognitive affective syndrome (CCAS/Schmahmann syndrome) and the neuropsychiatry of the cerebellum, emerge from this more complete and nuanced understanding of cerebellar function.
[Cerebellar cognitive affective syndrome (CCAS) is characterized by deficits in executive function, linguistic processing, spatial cognition and affect regulation (Schmahmann and Sherman, 1998). It arises from damage to the cognitive cerebellum in the cerebellar posterior lobe (lobules VI, VII, possibly lobule IX), and is postulated to reflect dysmetria of thought analogous to the dysmetria of motor control from damage to the sensorimotor cerebellum in the anterior lobe (lobules III–V) and lobule VIII].
4 figures including fMRI
7. Granella F, Tsantes E, Graziuso S, Bazzurri V, Crisi G, Curti E. Spinal cord lesions are frequently asymptomatic in relapsing–remitting multiple sclerosis: a retrospective MRI survey. J Neurol. 2019;266(12):3031-3037. doi:10.1007/s00415-019-09526-3
Recent guidelines recommend MRI imaging of the whole spinal cord (SC-MRI) at diagnosis, especially in patients who do not fulfil brain MRI criteria for dissemination in space. However, the role of SC-MRI in evaluating disease evolution and response to disease-modifying treatments (DMTs) is not well established. This is due partially to technical limitations in SC visualization and to economical constraints. In addition, whereas new brain lesions are often clinically silent and correlate well with future relapse risk, many MS experts consider the occurrence of asymptomatic new SCLs to be rare. Therefore, SC-MRI may not be recommended for routine follow-up in MS.
The aim of the present study was to investigate the frequency of asymptomatic SC combined unique activity (CUA, new/enlarging T2 or gadolinium-positive [Gd+] lesions) on MRI in a cohort of patients diagnosed with clinically isolated syndrome (CIS) or relapsing–remitting MS (RRMS).
In 340 SC-MRI scans with SC-CUA (230 patients), SC-CUA was asymptomatic in 31.2%; 12.1% of SC-CUA had neither clinical activity nor brain radiological activity.
A substantial proportion of the patients had SC-CUA without clinical symptoms and/or without concomitant brain MRI activity. In these patients, SC-CUA was the only sign of disease activity, suggesting that regular SC-MRI followup is required for reliable assessment of radiological activity and may improve the management of patients with MS.
The authors conclude that the results show that a consistent percentage of patients with active SCLs remained asymptomatic. In some of these patients, asymptomatic SCLs represented the only sign of disease reactivation. Thus, regardless of brain MRI activity, SC-MRI should be performed at follow-up because the prognostic value of SC involvement, isolated or concomitant with brain lesions, is a crucial factor in making treatment decisions.
2 tables, 2 figures, no images
8. Alawieh A, Chatterjee AR, Vargas J, et al. Lessons Learned Over More than 500 Stroke Thrombectomies Using ADAPT With Increasing Aspiration Catheter Size. Neurosurgery. 2020;86(1):61-70. doi:10.1093/neuros/nyy444
Although earlier trials on endovascular thrombectomy were performed using stent retrievers, recently completed the contact aspiration vs stent retriever for successful revascularization (ASTER) and a comparison of direct aspiration versus stent retriever as a first approach (COMPASS) trials have shown the noninferiority of direct aspiration.
The authors reviewed a retrospective database of AIS patients who underwent ADAPT thrombectomy (Direct Aspiration Approach as First Pass Technique) between January 2013 and November 2017 at the Medical University of South Carolina. Demographics and baseline characteristics, technical variables, and radiological and clinical outcomes were reviewed.
Among 510 patients (mean age: 67.7, 50.6% females), successful recanalization at first pass was achieved in 61.8%, and with aspiration only in 77.5%. Mean procedure time was 27.4 min, and the rate of good outcomes (mRS 0-2) at 90 d was 42.9%. The rate of recanalization with aspiration only was significantly higher, and procedure time was significantly lower in patients treated with larger catheters compared to smaller catheters. There were no differences in complication rates or postoperative parenchymal hemorrhage across groups. The use of ACE 068 was an independent predictor of good outcomes at 90 d on multivariate regression analysis.
Refinement of ADAPT thrombectomy by incorporating reperfusion catheters with higher inner diameters and thus higher aspiration forces is associated with better outcomes, shorter procedure times, and lower likelihood of using additional devices without impacting complication rates.
3 figures, 3 tables
