1. Chen JJ, Bhatti MT. Clinical phenotype, radiological features, and treatment of myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) optic neuritis. Curr Opin Neurol 2020;33:47–54
Optic neuritis is the most common cause of optic neuropathy in young patients, which can cause debilitating vision loss and blindness. Two novel glial autoantibodies have been discovered that better characterize a subset of patients with optic neuritis. In 2004, an antibody against an astrocytic water channel, aquaporin-4 (AQP4) was found, which greatly improved our understanding and diagnosis of the clinical entity that was previously termed Devic Disease but is now known as neuromyelitis optica spectrum disorders (NMOSD). More recently, serum antibodies specific for myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG), have been found in a subset of patients with optic neuritis and other demyelinating phenotypes. The phenotype of MOG IgG-associated disorder (MOGAD) is broad and includes optic neuritis, transverse myelitis, and acute demyelinating encephalomyelitis (ADEM). Optic neuritis is the most common presentation in adults, whereas ADEM is the most common presentation in children. Clinical characteristics suggestive of MOG-IgG optic neuritis include recurrent optic neuritis, prominent disc edema, and perineural enhancement of the optic nerve on MRI. Although the nadir of vision loss is severe with MOG-IgG optic neuritis, the recovery is typically better than AQP4-IgG optic neuritis and therefore has a favorable overall prognosis. Patients with relapsing disease will often need chronic immunotherapy. Rituximab, azathioprine, mycophenolate mofetil, and monthly intravenous immune globulin are the most commonly utilized treatments.
Although AQP4-IgG and MOG-IgG optic neuritis are important to recognize, the majority of optic neuritis in the Western world are from MS or remain idiopathic. Therefore testing AQP4-IgG and MOG IgG on every patient with optic neuritis may be low yield and could potentially generate false positives. However, because AQP4-IgG positivity changes management with the need for chronic immunotherapy, testing for AQP4-IgG should be considered for any optic neuritis, unless a patient has classic optic neuritis in the setting of demyelinating disease very suggestive of MS.
2 figures, 1 table
2. Ly KI, Wen PY, Huang RY. Imaging of central nervous system tumors based on the 2016 World Health Organization Classification. Neurol Clin 2020;38:95–113
This is a review article which takes a slightly different organization approach by describing different tumor types in relation to the 4 major headings of anatomic MR imaging, DWI and PWI, MRS, and machine learning. This is done for each of the glioma types with IDH mutation, 1p/19q codeletion, MGMT promoter methylation, and also for medulloblastomas.
As an example:
IDH-mut gliomas show a predilection for involvement of a single cerebral lobe, particularly the frontal lobe. By contrast, IDH-wt tumors tend to involve multiple lobes and have a more central and infratentorial location. This includes a higher proportion of IDH-wt tumors in the brainstem, which may reflect the presence of undiagnosed histone H3K27M-mutated tumors, a group of predominantly pediatric and highly aggressive tumors that, by definition, are exclusively IDH-wt. On T1W post-contrast sequences, IDH-mut tumors, including IDH-mut GBMs, typically demonstrate less enhancement.
Multiple retrospective studies have shown that the ADCmin is lower in grade II and III IDH-wt gliomas compared to IDH-mut counterparts of the same grade which likely reflects higher tumor cellularity and increased tumor aggressiveness of IDH-wt tumors.
The presence of D-2HG (2-hydroxyglutarate, the oncometabolite produced as a result of the IDH mutation) in IDH-mut gliomas has proved to be a valuable imaging biomarker. D-2HG is virtually absent in IDH-wt tumors but can reach high concentrations between 5 and 30 mM in IDH-mut cells, thus providing a high contrast/noise ratio between mutant cells and background.
Multiple studies suggest that IDH-mut and IDH-wt tumors can be differentiated based on quantitative MRI features, with accuracies ranging from 80% to 89%. In one study, a model that combined patient age, enhancement intensity, tumor volume/edema ratio, and multiple texture features predicted IDH status with an accuracy of up to 89%.
6 figures, 3 tables
3. Miyakawa T. No raw data, no science: another possible source of the reproducibility crisis. Mol Brain 2020;13:24. Available from: https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-020-0552-2
The reproducibility or replicability crisis is a serious issue in which many scientific studies are difficult to reproduce or replicate. It is reported that, in the field of cancer research, only about 11-25% of published studies could be validated or reproduced, and that only about 36% were reproduced in the field of psychology. Inappropriate practices of science, such as HARKing (hypothesizing after the results are known), p-hacking (researchers try out several statistical analyses and/or data eligibility specifications and then selectively report those that produce significant results), selective reporting of positive results and poor research design, have been proposed to be a cause of such irreproducibility. Here, the author argues that a lack of raw data is another serious possible cause of irreproducibility, by showing the results of analyses on the manuscripts that he handled over the last 2 years for the journal Molecular Brain.
As Editor-in-Chief of Molecular Brain, Dr. Miyakawa has handled 180 manuscripts since early 2017 and made 41 editorial decisions categorized as “Revise before review,” requesting that the authors provide raw data. Surprisingly, among those 41 manuscripts, 21 were withdrawn without providing raw data, indicating that requiring raw data drove away more than half of the manuscripts. He rejected 19 out of the remaining 20 manuscripts because of insufficient raw data. Thus, more than 97% of the 41 manuscripts did not present the raw data supporting their results when requested by an editor, suggesting a possibility that the raw data did not exist from the beginning, at least in some portions of these cases.
But wait, it gets better!
Among the 40 withdrawn or rejected manuscripts, 14 were later published in other journals. Twelve journals out of those that published the 14 papers require or recommend that the authors provide raw data upon request from readers in their policies. Therefore, he sent emails and printed letters to the authors of the 12 papers in those journals requesting raw data for the results in a Figure in the papers. Ten of the authors of the 12 papers did not respond to the request. The one who responded sent raw data only for one sample per condition, while each condition was supposed to have 6 samples. Another one who responded declined to send the raw data, because of some recently discovered “novel information”.
He concludes that institutions, funding agencies, and publishers should cooperate and try to support such a move by establishing data storage infrastructure to enable the securing and sharing of raw data, based on the understanding that “no raw data, no science.”
Additional source regarding p-hacking:
The Extent and Consequences of P-Hacking in Science
Head ML, Holman L, Lanfear R, et al. The extent and consequences of p-hacking in science. PLOS Biology 2015;13:e1002106. https://doi.org/10.1371/journal.pbio.1002106
4. Youngerman BE, Save AV, McKhann GM. Magnetic resonance imaging-guided laser interstitial thermal therapy for epilepsy: systematic review of technique, indications, and outcomes. Neurosurgery 2020;86:E366–82
Stereotactic ablation offers less invasive access to the epileptogenic zone (EZ) compared with surgical resection, especially for targets that are deep to uninvolved brain. Stereotactic chemical lesioning, cryoablation, and radiofrequency thermocoagulation (RF-TC) of the amygdala and hippocampus for epilepsy were first reported in the 1960s and 1970s with variable results. Computed tomography (CT)- and magnetic resonance imaging (MRI)-guided radiofrequency thermocoagulation in the 1990s brought improved targeting and safety, and it is still practiced at select centers, but open resection remained the preferred approach for most surgeons and indications. Laser interstitial thermal therapy (LITT) allowed larger yet more discrete lesions. Human laser interstitial thermal therapy was first performed for liver metastases and, in the brain, for gliomas and cerebral metastases in the early 1990s. In parallel, MR thermometry demonstrated that time-dependent tissue damage occurs between certain temperature thresholds. Improvements in imaging paved the way for modern systems that, in near real time, accurately monitor temperature, track cumulative dose delivery, and estimate tissue damage on and off target. Commercial MR-guided laser interstitial thermal therapy (MRgLITT) was Food and Drug Administration (FDA) cleared in 2007 for use in neurosurgery and first reported for treatment of drug-resistent epilepsy in 2012. The authors provide an overview of the technique, as well as specific applications for mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasia, tuberous sclerosis, periventricular nodular heterotopia and cavernous malformations.
6 figures, 4 tables
5. Badhiwala JH, Ahuja CS, Akbar MA, et al. Degenerative cervical myelopathy — update and future directions. Nat Rev Neurol 2020;16:108–24. Available from: http://dx.doi.org/10.1038/s41582-019-0303-0
Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction. This clinicopathological entity is characterized by acquired stenosis of the cervical spinal canal (with or without superimposed congenital stenosis) secondary to osteoarthritic degeneration (for example, cervical spondylosis) or ligamentous abnormalities (for example, ossification of the posterior longitudinal ligament (OPLL)) of the spinal column. The condition can be likened to osteoarthritis of the knee or hip, but besides pain, DCM can lead to progressive disability and paralysis owing to chronic spinal cord compression and non- traumatic spinal cord injury.
A few key points in this extensive review:
DCM is the most common cause of spinal cord impairment, and the resultant burden of disability on our society is expected to grow owing to the ageing global population.
The pathophysiology of DCM involves static and dynamic factors that lead to chronic spinal cord compression and resultant ischemia, inflammation and apoptosis of neurons and oligodendrocytes.
The natural history of DCM can include a period of stable neurological status in some patients; however, a substantial number of individuals experience progressive, stepwise decline in function.
Current clinical practice guidelines recommend surgical decompression for patients with severe or moderate DCM and either surgery or a supervised trial of structured rehabilitation in patients with mild DCM.
Traditionally, the main goal of operative intervention for DCM was to maintain current neurological status and prevent further deterioration. However, evidence from the past decade suggests that surgical decompression can improve neurological function. To date, the AOSpine CSM North America (CSM- NA) and AOSpine CSM International (CSM- I) studies are the largest prospective investigations of clinical outcomes after decompressive surgery for DCM. Both studies demonstrated that surgery significantly improves long term (>1 year) neurological function, disability and health- related quality of life. The greatest improvements were seen in patients with moderate or severe DCM at presentation.
5 figures, 2 tables
6. Ius T, Cesselli D, Isola M, et al. Incidental low-grade gliomas: single-institution management based on clinical, surgical, and molecular data. Neurosurgery 2019;86:18–24
7. Patel NV, Langer DJ, Boockvar JA. Commentary: incidental low-grade gliomas: single institution management based on clinical, surgical, and molecular data. Neurosurgery 2019;86:258–59
The authors of this study examine their intra-institutional LGG cohort in a retrospective fashion and compare incidental (iLGG) to symptomatic (sLGG) cases (thirty-four iLGG cases were identified within a mono-institutional cohort of 332 patients operated for low-grade gliomas from 2000 to 2017). The authors specifically assess lesional volume, anatomical location, Karnofsky Performance Scores (KPS), extent of resection (EOR), and molecular characteristics. The findings suggest that surgery for iLGG trends toward better outcomes due to smaller volumes, non-eloquent locations, and increased extent of resection.
There is no existing standardized approach for LGG management. Algorithms vary and some operators stratify patients and decision-making based on age of diagnosis. For LGG, extent of resection can predict overall survival (OS). Achieving > 90% extent of resection led to a 90% to 97% overall survival at 5 yr; EOR < 90% had rates 60% to 76%. The role for adjuvant therapy, such as chemotherapy and radiation, is also variable. In older patients and those with subtotal resection, radiation is recommended. Drugs such as TMZ and procarbazine/ lomustine/ vincristine (PCV) have been employed with success for LGG. A significant increase in OS with PCV and radiation vs. radiation alone has been shown. It seems the field-wide approach to LGGs is standardizing towards surgical resection and molecular classification followed by adjuvant therapy.
2 figures, 2 tables
8. Maeda FL, Formentin C, de Andrade EJ, et al. Reliability of the new AOSpine classification system for upper cervical traumatic injuries. Neurosurgery 2020;86:E263–70. Available from: https://academic.oup.com/neurosurgery/article-abstract/86/3/E263/5603214?redirectedFrom=fulltext
The new AOSpine Upper Cervical Classification System (UCCS) was recently proposed by the AOSpine Knowledge Forum Trauma team to standardize the treatment of upper cervical traumatic injuries (UCI). In this context, evaluating its reliability is paramount prior to clinical use.
This system is an extrapolation from the other AOSpine classifications, which divide injuries according to the affected region(s) (injury sites): I, injuries involving the occipital condyles and the craniocervical junction; II, injuries involving the atlas and the atlantoaxial joint; and III, injuries involving the axis and the C2-3 joint.
These 3 locations were then subdivided into 3 types, similar to the AOSpine classifications for subaxial cervical spine, thoracic, and lumbar trauma: type A (stable), bony injury only, without significant ligamentous, tension band, or disc injury; type B (stable or unstable), tension band/ligamentous injury, with or without bony injury, without complete separation of anatomic integrity; and type C (unstable), significant translation in any directional plane and separation of anatomic integrity.
A total of 32 patients with UCI treated either nonoperatively or with surgery by one of the authors were included in the study. Injuries were classified based on the new AO UCCS according to site and injury type using computed tomography scan images in 3 planes by 8 researchers at 2 different times, with a minimum interval of 4 weeks between assessments. Intra- and interobserver reliability was assessed using the kappa index (K). Intraobserver agreement for sites ranged from 0.830 to 0.999, 0.691 to 0.983 for types, and 0.679 to 0.982 for the recommended treatment.
This study reported an acceptable reproducibility of the new AO UCCS and safety in recommending the treatment. Further clinical studies with a larger patient sample, multicenter and international, are necessary.
2 figures, 4 tables
