Journal Scan – This Month in Other Journals, November 2020

1. Salem MM, Ravindran K, Enriquez-Marulanda A, et al. Pipeline embolization device versus stent-assisted coiling for intracranial aneurysm treatment: a retrospective propensity score-matched study. Neurosurgery 2020;87:516–22

No studies have been done using propensity score to match small unruptured anterior circulation aneurysms (<10 mm), where controversy regarding the most appropriate treatment method exists. The aim of this study was to comparatively assess the efficacy of the Pipeline embolization device (PED) and stent-assisted coiling (SAC) via propensity score matching (PSM) in aneurysms deemed amenable to both modalities, controlling for both baseline and aneurysm characteristics.

The authors conducted a retrospective analysis of patients with aneurysms treated at their institution with either PED from 2013 to 2017 or SAC from 2009 to 2015. All large (>10 mm), ruptured, fusiform, anterior communicating artery, posterior circulation aneurysms, and patients with no available follow-up imaging were eliminated before running the propensity score matching (PSM). Patients were matched using nearest neighbor controlling for: age, gender, smoking, exact location, maximal diameter, and presence of multiple aneurysms. Total hospital costs for equipment and implants were calculated.

Out of 165 patients harboring 202 aneurysms; 170 (84.2%) were treated with the PED, and 32 (15.8%) were treated using SAC. PSM resulted in 23 matched pairs; with significantly longer follow up in the SAC group (mean 29.8 vs 14.1 mo; P = .0002). Complete occlusion rates were not different (82.6 vs 87%), with no difference between the groups for modified Rankin Scale on last clinical follow-up, procedural complications or retreatment rates. Average total costs calculated from the hospital records, including equipment and implants, were not different between propensity-score matched pairs.

PED placement and SAC offer equally efficacious occlusion rates, functional outcomes, procedural complication rates, and cost profiles for small unruptured anterior circulation saccular aneurysms which do not involve the anterior communicating artery.

4 tables

2. Bendtsen L, Zakrzewska JM, Heinskou TB, et al. Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia. Lancet Neurol 2020;19:784–96. Available from: http://dx.doi.org/10.1016/S1474-4422(20)30233-7

In 2018, both the International Headache Society (HIS) and International Association for the Study of Pain (IASP) published new classifications for trigeminal neuralgia in an effort to align the two classifications. Although the two classifications differ in format, the classifications are similar with regard to the clinical characteristics required for diagnosis. According to the third edition of the International Classification of Headache Disorders, trigeminal neuralgia is defined by recurrent severe paroxysmal pain restricted to the trigeminal territory, lasting from a fraction of a second up to 2 min, with the pain described as electric shock-like, stabbing, or sharp, and being triggered by innocuous stimuli.

What was previously termed classical trigeminal neuralgia is now termed either classical or idiopathic trigeminal neuralgia in both classifications, depending on whether there is a neurovascular contact with morphological changes of the trigeminal nerve on the symptomatic side. Trigeminal neuralgia caused by other pathological characteristics, such as tumors in the CP angle or multiple sclerosis, is now termed secondary trigeminal neuralgia.

–Idiopathic trigeminal neuralgia: no diagnostic tests confirming lesion or disease that can explain trigeminal neuralgia

–Classical trigeminal neuralgia: demonstration of vascular compression with morphological changes of the trigeminal nerve root on MRI or during surgery

–Secondary trigeminal neuralgia: demonstration of underlying disease known to be able to cause neuralgia by MRI or other diagnostic test—eg, tumour in the cerebellopontine angle, arteriovenous malformation, and multiple sclerosis

-Idiopathic and classical trigeminal neuralgia are further subclassified into groups with purely paroxysmal pain or with concomitant continuous pain on the basis of pain phenotype

The symptomatology of trigeminal neuralgia is essentially the same across all known causes—ie, classical, idiopathic, and secondary trigeminal neuralgia. There is converging evidence of neural pathology at the root entry zone resulting from its compression by a blood vessel or tumor.  Within this zone, the transition of peripheral Schwann cell myelination to central oligodendroglia myelination takes place, which is thought to make the entry zone particularly susceptible to pressure. Biopsy specimens obtained from the compressed region at operation, show demyelination, dysmyelination, and remyelination, and direct apposition of demyelinated axons. It is well established that demyelinated afferents tend to become hyperexcitable and capable of generating ectopic impulses manifesting as spontaneous pain.

Neuroimaging, especially MRI, is essential for the etiological subclassification of clinically identified trigeminal neuralgia into either primary trigeminal neuralgia or secondary trigeminal neuralgia typically caused by multiple sclerosis or a space-occupying lesion in the prepontine cistern. A combination of three high-resolution sequences: three-dimensional (3D) T2-weighted, 3D time-of-flight MR angiography along with 3D T1-weighted C+ has proved to be reliable in detecting vascular contact and in predicting the degree of root compression.

2 figures, 2 tables with 1 MR

3. Yuste R, Hawrylycz M, Aalling N, et al. A community-based transcriptomics classification and nomenclature of neocortical cell types. Nat Neurosci 2020;83:1284–302. Available from: http://www.nature.com/articles/s41593-020-0685-8

To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, the authors propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature.

Recent advances in high-throughput single-cell transcriptomics (scRNAseq) have changed the paradigm of cellular classification, offering a new quantitative genetic framework. These approaches measure the expression profiles of thousands of genes from individual cells in large numbers, at relatively high speed and low cost. Related methods in epigenomics can identify sites of methylation and putative gene transcriptional regulation, essential to cell function and state. These new methods are an outcome from the methodological, conceptual and economic revolution created by the Human Genome Project and have flourished with support from the BRAIN Initiative. With genomes in hand, it is now feasible to generate entire transcriptomes (which include the sequence and structure of transcripts) from tissues and to scale these methods for amplifying RNA in single cells.

Extensive and complex review with useful introduction on the history of cell type classifications.

5 large and largely incomprehensible (to me) figures

4. Butscheidt S, Ernst M, Rolvien T, et al. Primary intraosseous meningioma: clinical, histological, and differential diagnostic aspects. J Neurosurg 2019;133:1–10. Available from: https://thejns.org/view/journals/j-neurosurg/aop/article-10.3171-2019.3.JNS182968.xml

In the years 2009–2017, 26 cases of PIM were diagnosed using MRI and CT scans. In 16 cases the indication for resection was given, and specimens were further examined using a multilevel approach, including histological and immunohistochemical analyses. Additionally, the local database was searched for all cases of meningiomas, as well as osteosclerotic differential diagnoses—i.e., fibrous dysplasia, Paget’s disease of bone, and other benign osteosclerotic lesions.

PIM represented 2.4% of all meningiomas with a predominant occurrence in females (85%). Regarding the initial manifestation, PIMs show a slightly earlier onset than meningiomas. While most PIMs are located in the sphenoid bone, associated calcifications were visible in 58% of the cases on CT scans. Most of the cases were classified as WHO grade I (93%) and meningotheliomatous meningiomas (91%). Tumor growth was associated with an increased bone resorption followed by massive osteoid deposition and consecutive sclerosis.

The authors point out two major consequences of their analysis: first, they support the theory of hyperostotic changes being directly connected to tumor invasion, which elucidates the need for wide total resections, including the radiolucent borderlines; second, the bone turnover (i.e., osteoclast and osteoblast activity) may play a central role in the tumor growth. Therefore, antiresorptive drugs such as bisphosphonates should be considered as adjuvant treatment concepts. A previous case report observed a reduction in the clinical symptoms as well as in the scintigraphic uptake of the skull region after the administration of etidronate 200 mg/day for 6 months. Particularly those patients who are not amenable to total resection procedures may benefit from such approaches.

5 figures including histology and MR

5. Tan AC, Ashley DM, López GY, et al. Management of glioblastoma: state of the art and future directions. CA Cancer J Clin 2020;70:299–312

Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years, and 5-year survival <10%. There is a slight predominance in males, and incidence increases with age. The standard approach to therapy in the newly diagnosed setting includes surgery followed by concurrent radiotherapy with temozolomide and further adjuvant temozolomide. Tumor-treating fields, delivering low-intensity alternating electric fields, can also be given concurrently with adjuvant temozolomide. At recurrence, there is no standard of care; however, surgery, radiotherapy, and systemic therapy with chemotherapy or bevacizumab are all potential options, depending on the patient’s circumstances.

The recently revised classification of glioblastoma based on molecular profiling, notably isocitrate dehydrogenase (IDH) mutation status, is a result of enhanced understanding of the underlying pathogenesis of disease. IDH–wild-type glioblastoma corresponds to the clinically defined primary glioblastoma characterized by de novo development with no identifiable precursor lesion. This cohort represents the overwhelming majority of patients with glioblastoma (approximately 90%), is more commonly diagnosed in older patients, and has a more aggressive clinical course. Conversely, IDH-mutant glioblastoma or secondary glioblastoma typically arises from a precursor diffuse or anaplastic astrocytoma. This cohort represents approximately 10% of patients, it predominates in younger patients with a median age at diagnosis of 44 years, and it generally carries a better prognosis. The World Health Organization 2016 classification also added a new subtype under grade IV gliomas:  H3-K27M-mutant, diffuse midline gliomas. They occur predominantly in children and young adults and are characterized by an extremely poor prognosis. These tumors may have previously been classified as glioblastomas but are now considered a distinct and separate entity.

In the recurrent setting, GTR, if feasible, should be considered, particularly if >6 months have elapsed since the initial surgery and in younger patients with good performance status. A subgroup analysis of the DIRECTOR trial indicated that survival and quality of life may be improved with GTR. There have been no randomized trials specifically investigating the survival benefit of surgery in the recurrent setting.

There is a clear need for better therapeutic options, and there have been substantial efforts exploring immunotherapy and precision oncology approaches. In contrast to other solid tumors, however, biological factors, such as the blood-brain barrier and the unique tumor and immune microenvironment, represent significant challenges in the development of novel therapies.

3 figures with MR

6. Finck T, Liesche-Starnecker F, Probst M, et al. Bornavirus encephalitis shows a characteristic MR phenotype in humans. Ann Neurol 2020;88:723–35. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.25873

The authors retrospectively analyzed 55 MRI exams of 19 patients with confirmed Borna disease virus (BoDV-1) encephalitis. Fifty brain regions were systematically analyzed (T1w, T2w, T2*w, T1w + Gd, DWI) in order to discern a specific inflammation pattern. Histopathological analysis of 25 locations of one patient served as correlation for MRI abnormalities.

Baseline imaging, acquired at a mean of 11 ± 10 days after symptom onset, as well as follow-up scans of 16 patients revealed characteristic T2-hyperintensities with predilection for the head of the caudate nucleus, insula and cortical spread to the limbic system, whereas occipital lobes and cerebellar hemispheres were unaffected. This gradient was confirmed by histology.

3 MR figures, 4 tables

7. Patel PD, Canseco JA, Houlihan N, et al. Overview of minimally invasive spine surgery. World Neurosurg 2020;142:43–56. Available from: https://doi.org/10.1016/j.wneu.2020.06.043

Of the numerous forms of MISS, 3 techniques deserve special consideration:

1) mini-open/percutaneous, 2) tubular, and 3) endoscopic. Although each confers its own advantages and disadvantages, all 3 continue to evolve and expand their indications. The present review aims to consolidate the literature on the modern state of MISS, focusing on these main options, and addressing their strengths and shortcomings in different settings.  Cervical, thoracic and lumbar are covered as well as the use of MISS in deformity, tumors and trauma.

Advancements in tailored interbody cages and 3D-printed biomodels continue to support the drive of MISS toward patient-specific interventions. Furthermore, agencies have realized the financial benefits of MISS, as shown by the recent increased reimbursement on minimally invasive sacroiliac joint fusions by the Centers of Medicare and Medicaid Services. MISS is a feasible and effective alternative to conventional open approaches; however, the use of these techniques is depends on the expertise and clinical judgment of the surgeon and the patient’s clinical presentation.

5 figures, 1 table

8. Endisch C, Westhall E, Kenda M, et al. Hypoxic-ischemic encephalopathy evaluated by brain autopsy and neuroprognostication after cardiac arrest. JAMA Neurol 2020 July 20. [Epub ahead of print] Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2768384

Following cardiac arrest (CA), the severity of hypoxic ischemic encephalopathy (HIE) determines neurologic outcome. In patients with suspected HIE, current guidelines recommend multimodal neuroprognostication. Bilaterally absent cortical somatosensory-evoked potentials (SSEPs), serum neuron-specific enolase (NSE) concentration above a critical threshold, highly malignant electroencephalographic (EEG) patterns, and a gray-white matter ratio (GWR) based on brain computed tomographic (CT) imaging findings >1.1 reliably estimate poor outcome. Neuroprognostication studies are susceptible to a self-fulfilling prophecy, as the findings shown with investigated prognostic parameters frequently influence decisions regarding withdrawal of life-sustaining therapy.

The authors studied brain autopsies of patients who experienced CA and investigated the association between the severity of histopathologic findings showing brain damage and premortem neuroprognostication.

Of 187 included patients, 117 were men (63%) and median age was 65 years. Severe HIE was found in 114 patients (61%) and no/mild HIE was identified in 73 patients (39%). Severe HIE was found in all 21 patients with bilaterally absent somatosensory-evoked potentials, all 15 patients with gray-white matter ratio less than 1.10 on brain computed tomographic imaging, all 9 patients with suppressed EEG, 15 of 16 patients with burst-suppression EEG, and all 29 patients with neuron-specific enolase levels greater than 67 μg/L more than 48 hours after CA without confounders.

In conclusion, they found severe HIE in patients with poor prognostic findings obtained from SSEP, brain CT imaging, EEG, and serum NSE levels, supporting the current practice to predict poor outcome after CA. However, for individual tests, the sample size was limited; thus, the results need corroboration in future studies.

4 figures with 1 table, with histology

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