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Table of Contents    
NI FEATURE: THE FIRST IMPRESSION - COMMENTARY
Year : 2018  |  Volume : 66  |  Issue : 6  |  Page : 1776-1792

A summary of some of the recently published, seminal papers in neuroscience


1 Department of Neurosurgery, Wockhardt Hospital and Sir JJ group of Hospitals, Mumbai, Maharashtra, India
2 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Radiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
4 Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
5 Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
6 Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
7 Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication28-Nov-2018

Correspondence Address:
Dr. Kuntal K Das
Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.246289

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How to cite this article:
Turel MK, Tripathi M, Aggarwal A, Singla N, Ahuja CK, Takkar A, Mehta S, Garg K, Yadav R, Mehrotra A, Das KK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India 2018;66:1776-92

How to cite this URL:
Turel MK, Tripathi M, Aggarwal A, Singla N, Ahuja CK, Takkar A, Mehta S, Garg K, Yadav R, Mehrotra A, Das KK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India [serial online] 2018 [cited 2018 Dec 14];66:1776-92. Available from: http://www.neurologyindia.com/text.asp?2018/66/6/1776/246289


Ziai H, et al. Impact of dural resection on sinonasal malignancies with skull base encroachment or erosion. J Neurol Surg B Skull Base 2018;79:419-6.

The authors conducted a study to determine the occult rate of dural invasion in patients with tumors extending to and/or eroding the bony anterior skull base but without the evidence of dural invasion on preoperative imaging; and, to determine the impact of dural resection of skull base erosion on survival outcomes in this group of 37 patients. The occult rate of dural invasion was 54%. Patients with dural resection had improved margin control versus those without dural resection (90% vs 56%). Dural resection improved the 5-year overall survival only in patients with an esthesioneuroblastoma, compared with bony skull base resection alone (100% vs 75%). They concluded that a substantial rate of occult dural invasion was present in these lesions despite the absence of overt imaging findings. Dural resection may be associated with improved margin control, but no oncologic benefit was seen in tumors except for esthesioneuroblastomas. However, the treatment heterogeneity and the small sample size may have limited their conclusions.

Contributed by Dr. Mazda K. Turel

Lobatto DJ, et al. Preoperative risk factors for postoperative complications in endoscopic pituitary surgery: A systematic review. Pituitary 2018;21:84-97.

The authors conducted a systematic review of the association between the preoperative characteristics and the postoperative complications related to endoscopic tran-sphenoidal surgery. In total, 23 articles containing 5491 patients (96% of them having a pituitary adenoma) were included. Consistently significant associations that were responsible for the occurrence of complications in general, included an older age group, and an intraventricular extension of the tumor [the latter was responsible for the development of cerebrospinal fluid (CSF) leak]. Associations identified in some but not all of the studies were a younger age; an increased body mass index; the female gender; a learning curve that was associated with a higher incidence of CSF leak; an increased tumor size; and, the presence of a Rathke's cleft cyst that was associated with a higher incidence of diabetes insipidus. Mortality (with an incidence of 1%) was not addressed as a risk factor. However, the authors concluded that the low-to-medium quality of the currently available literature was insufficient for unequivocally validating the incidence of risk factors responsible for the development of complications after endoscopic pituitary surgery.

Contributed by Dr. Mazda K. Turel

Nayak P, et al. Predictors of postoperative diabetes insipidus following endoscopic resection of pituitary adenomas. Endocr Soc 2018;2:1010-9.

The development of diabetes insipidus (DI) following trans-sphenoidal resection of pituitary adenomas has been associated with a higher postsurgical morbidity and a longer duration of hospitalization. The authors evaluated the incidence of DI following pituitary adenoma resection and assessed the preoperative risk factors that were associated with postoperative DI in 271 patients undergoing endoscopic endonasal resection of a pituitary adenoma. The incidence of DI was 16%, with only 4% of the patients going on to develop a permanent DI. The presence of visual abnormalities, suprasellar extension, and a large tumor diameter were significantly associated with an increased incidence of postoperative DI. Hyperprolactinemia, tumor functionality, and cerebrospinal fluid exposure were not found to be significant contributors. Patients harbouring these factors warrant a closer postoperative monitoring as well as an adequate preoperative counselling, keeping in mind the higher likelihood of development of postoperative DI in these patients.

Contributed by Dr. Mazda K. Turel

Reinshagen C, et al. CRISPR-enhanced engineering of therapy-sensitive cancer cells for self-targeting of primary and metastatic tumors. Sci Transl Med 2018;11;10.

Tumor cells engineered to express therapeutic agents have shown a promise in the treatment of cancer. However, their potential to target cell surface receptors specific to the tumor site and their posttreatment fate have not been explored. The authors created therapeutic tumor cells that expressed ligands specific to the primary and recurrent tumor sites (receptor self-targeted tumor cells) and extensively characterized two different approaches using (i) therapy-resistant cancer cells, engineered with secretable death receptor-targeting ligands for “off-the-shelf” therapy in primary tumor settings; and, (ii) therapy-sensitive cancer cells, which were CRISPR [clustered regularly interspaced short palindromic repeats]-engineered to knock out therapy-specific cell surface receptors, before engineering them with receptor self-targeted ligands, and being reapplied in autologous models of recurrent or metastatic disease. They show that both approaches allow for a high expression of targeted ligands that induce tumor cell killing and translate into a marked survival benefit in mouse models of multiple cancer types. Safe elimination of the therapeutic cancer cells after treatment was achieved by co-engineering them with a prodrug-converting suicide system, which also allowed for real-time in-vivo positron emission tomography imaging to determine the fate of therapeutic tumor cells. This study demonstrates a self-tumor tropism of engineered cancer cells and their therapeutic potential when engineered with receptor self-targeted molecules, and establishes a roadmap towards a safe clinical translation of this therapy for different cancer types in the primary, recurrent, and metastatic setting.

Contributed by Dr. Mazda K. Turel

Kepka L, et al. Quality of life after whole brain radiotherapy compared with radiosurgery of the tumor bed: Results from a randomized trial. Clin Transl Oncol 2018;20:150-9.

A recent randomized trial demonstrated no difference in the neurocognitive function between stereotactic radiotherapy of the tumor bed (SRT) and whole brain radiotherapy (WBRT) in patients with resected single brain metastasis. Patients treated with SRT had a lower overall survival compared with the WBRT arm. In this study, the authors compared the health-related quality of life (HRQOL) in patients who received WBRT vs. SRT. Of the 59 randomized patients, 37 (64%) were eligible for the HRQOL analysis, and 15 received SRT and 22 received WBRT. There were no differences between the groups in their global health status and main function scales/symptoms (except for drowsiness and appetite loss, which were worse with WBRT, 2 months after the administration of radiotherapy [RT]). The global health status decreased 2 and 5 months after the administration of RT, but a significant change was only obtained when SRT was administered. After the administration of SRT, their physical functions decreased significantly after 5 months. The ‘future uncertainty’ worsened after RT, but the result was significantly worse after 2 months following the administration of SRT. Patients treated with WBRT had a significant worsening of appetite, hair loss, and drowsiness after treatment. Despite a higher symptom burden after WBRT attributed to the side effects of RT (such as appetite loss, drowsiness, and hair loss), the global health status, physical functioning, and future uncertainty favored WBRT compared with SRT of the tumor bed. This may be related to the compromised brain tumor control produced as a result of the omission of WBRT.

Contributed by Dr. Mazda K. Turel

Chhipa RR, et al. AMP kinase promotes glioblastoma bioenergetics and tumour growth. Nat Cell Biol 2018;20:823-35

Stress is integral to tumour evolution, and the cancer cell survival depends on the stress management. The authors found that cancer-associated stress chronically activates the bioenergetic sensor adenosine monophosphate (AMP)-activated kinase (AMPK) and, to survive, tumour cells hijack an AMPK-regulated stress response pathway conserved in normal cells. Analysis of ‘The Cancer Genome  Atlas More Details’ data revealed that AMPK isoforms are highly expressed in the lethal human cancer glioblastoma (GBM). They show that the AMPK inhibition reduces the viability of patient-derived GBM stem cells (GSCs) and tumours. In stressed (exercised) skeletal muscle, AMPK is activated to cooperate with CREB1 (cAMP response element binding protein-1) and promotes glucose metabolism. The data also demonstrated that oncogenic stress chronically activates AMPK in GSCs that co-opt the AMPK-CREB1 pathway to coordinate tumour bioenergetics through the transcription factors hypoxia-inducible factor 1-alpha (HIF1α) and GA binding protein transcription factor subunit A (GABPA). Finally, the data shows that adult mice tolerate the systemic deletion of AMPK, supporting the use of AMPK pharmacological inhibitors in the treatment of GBM. This study in fact has indicated that the protein AMPK may be a key driver of glioblastoma growth, contrary to a previous research which has suggested it as a suppressor of tumour growth.

Contributed by Dr. Mazda K. Turel

Ostrom QT, et al. Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21. Sci Rep 2018;8:7352.

The incidence of glioma is approximately 50% higher in male patients. The previous glioma genome-wide association studies (GWAS) have not stratified gender-wise incidences. The potential gender-specific genetic effects were assessed in autosomal single nucleotide polymorphisms (SNPs) and in sex chromosome variants in all patients harbouring a glioma, or a glioblastoma, and also in non-GBM patients using data from four previously published glioma GWAS. Datasets were analysed using gender-stratified logistic regression models and combined using a meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) location in the male patients only. An association at rs55705857 (8q24.21) was stronger in the female patients than in the male ones. A large region on 3p21.31 was identified with significant association in the female patients only. The identified differences between the effect of the risk variants do not fully explain the observed gender-based differences in the incidence of development of a glioma. It is hoped that the assessment of genetic sources of gender-based differences in brain tumours may help to assess/predict the risk of developing brain tumours in the future.

Contributed by Dr. Mazda K. Turel

Lee JH, et al. Human glioblastoma arises from sub-ventricular zone cells with low-level driver mutations. Nature 2018;560:243-7.

A glioblastoma (GBM) is a devastating and an incurable brain tumour. Identification of the cell of origin of the tumor that harbours the mutations that are driving the genesis of gliomas, could provide a fundamental basis for understanding the disease progression and in developing new treatment strategies. Studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the sub-ventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates. The authors in this paper describe direct molecular and genetic evidences from human brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, they performed a deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients harbouring either an isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumours. They found that the normal SVZ tissue away from the tumour, in 56% of patients with wild-type IDH GBM, contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of the patient brain tissue and the genome editing of a mouse model, they found that astrocyte-like NSCs that carry driver mutations, migrate from the SVZ and lead to the development of high-grade malignant gliomas in the distant brain regions. Together, their results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations responsible for the development of a GBM.

Contributed by Dr. Mazda K. Turel

Kheirkhah P, et al. Magnetic drug targeting: A novel treatment for intramedullary spinal cord tumors. Sci Rep 2018;8:11417

Most applications of nanotechnology in cancer have focused on the systemic delivery of cytotoxic drugs. Systemic delivery relies on the accumulation of nanoparticles in a target tissue through an enhanced permeability of the leaky vasculature and the retention effect of a poor lymphatic drainage to increase the therapeutic index. The systemic delivery is limited, however, by toxicity and difficulty in crossing the natural obstructions, like the blood-spine barrier. Magnetic drug targeting (MDT) is a new technique to reach tumors of the central nervous system. The authors describe a novel therapeutic approach for high-grade intramedullary spinal cord tumors using magnetic nanoparticles (MNP). Using biocompatible compounds that form a superparamagnetic carrier, and using magnetism as a physical stimulus, MNP-conjugated with doxorubicin were successfully localized to a xenografted tumor in a rat model. This study demonstrates a proof-of-concept that MDT may provide a novel technique for the effective and concentrated delivery of chemotherapeutic agents to intramedullary spinal cord tumors without the patients having to face the toxicity of systemic administration.

Contributed by Dr. Mazda K. Turel

Takase H, et al. Delayed C5 palsy after anterior cervical decompression surgery; Preoperative foraminal stenosis and postoperative spinal cord shift increase the risk of palsy. World Neurosurg 2018 doi: 10.1016/j.wneu.2018.08.240.

Postoperative C5-palsy is now a well-known complication after cervical decompression and the debate on its etiology continues. While the incidence of C5-palsy in posterior approaches to the cervical spine has been far more extensively studied, the purpose of this study was to clarify the risk factors for C5-palsy in the anterior approach. 88 cases were enrolled. Four sides of three individuals (4.6%) who underwent a multiple-level corpectomy developed C5-palsy. All paralyses became evident several days after the surgery and finally recovered. An older age, multiple-level corpectomy, postoperative spinal cord shift, and foraminal stenosis of C4-5 and C5-6 were statistically extracted as the causative factors of C5 palsy. In the patients who developed the C5-palsy, distortion of the anterior nerve roots due to a residual vertebral spur was observed with the anterior spinal cord-shift after the anterior corpectomy. In conclusion, an appropriate patient selection and sufficient additional foraminotomy should be undertaken while addressing extensive anterior lesions and locally developed kyphosis, to avoid the postoperative C5 palsy.

Contributed by Dr. Mazda K. Turel

Chughtai M, et al. Postoperative stroke after anterior cervical discectomy and fusion in patients with carotid artery stenosis: A state wide database analysis. Spine J 2018 doi: 10.1016/j.spinee.2018.09.011.

Carotid artery injury and stroke secondary to prolonged retraction remains an extremely rare complication in anterior cervical discectomy and fusion (ACDF). The authors aimed to evaluate: (1) the incidence of postoperative stroke following ACDF; and, (2) the incidence of other postoperative complications in a cohort of patients who had a diagnosis of carotid artery stenosis (CAS) versus those who did not. There were 34,975 patients who underwent an ACDF in the study period. There were 61 patients who had developed a CAS. These patients were compared to a propensity-matched cohort. The CAS cohort had a significantly higher incidence of postoperative stroke during their hospitalization (7% vs 0%). The CAS cohort also had a higher rate of acute renal failure (30% vs 5%,) and sepsis (18% vs 5%). There were no stroke related deaths. The patients with CAS who underwent ACDF had a significantly greater incidence of developing postoperative stroke. These results may illustrate the importance of pre-operative optimization, approach-selection, and postoperative stroke surveillance in patients with a history of CAS who undergo ACDF.

Contributed by Dr. Mazda K. Turel

Owens RK 2nd, et al. Back pain improves significantly following discectomy for lumbar disc herniation. Spine J 2018;18:1632-6.

The study aimed to determine if patients with lumbar disc herniation (LDH) with substantial back pain do improve with decompression alone. Patients enrolled in this study had baseline back pain scores of ≥5 out of 10. They underwent a single- or two-level lumbar discectomy only. Back and leg pain scores (0-10), Oswestry Disability Index (ODI), and EuroQoL 5D were measured. The mean age of the cohort was 50 years and 1,195 patients (52.8%) were male. The mean body mass index was 30.1 kg/m2. About half of the patients (1,103, 48.8%) underwent a single-level discectomy and the other half (1,159, 51.2%) had a two-level discectomy. The average length of stay was 0.53 days. At 3 and 12 months postoperatively, there were a statistically significant improvement in back pain (from 7.7 to 2.9 to 3.2), leg pain (from 7.5 to 2.3 to 2.5), and ODI (from 26.2 to 11.6 to 11.2). Patients with a single-level discectomy, compared with patients with a two-level discectomy, had similar improvements in the 3- and 12-month back pain, leg pain, and ODI scores. Thus, patients with LDH who have substantial back pain can be counselled to expect improvement in their back pain scores 12 months after a discectomy procedure.

Contributed by Dr. Mazda K. Turel

Patibandla MR, et al. Stereotactic radiosurgery for Spetzler-Martin Grade IV and V arteriovenous malformations: An international multicenter study. J Neurosurg 2018;129:498-507.

Due to the complexity of Spetzler-Martin (SM) Grade IV-V arteriovenous malformations (AVMs), the management of these lesions remains controversial. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after single-session stereotactic radiosurgery (SRS) for SM Grade IV-V AVMs and determine the predictive factors in 233 patients at 8 participating centers recruited in the International Gamma Knife Research Foundation study. Pre-SRS embolization was performed in 71 AVMs (30.5%). The mean nidus volume, SRS margin dose, and follow-up duration were 9.7 cm3, 17.3 Gy, and 84.5 months, respectively. At a mean follow-up interval of 84.5 months, a favorable outcome, defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RIC), was achieved in 26% of patients. The actuarial obliteration rates at 3, 7, 10, and 12 years were 15%, 34%, 37%, and 42%, respectively. The annual post-SRS hemorrhage rate was 3%. Only the larger AVM diameter was found to be an independent predictor of an unfavorable outcome in the multivariate logistic regression analysis. The rate of a favorable outcome was significantly lower for unruptured SM Grade IV-V AVMs compared with the ruptured ones.

Contributed by Dr. Mazda K. Turel

Kim DB, et al. Comparison of craniotomy and decompressive craniectomy in large supratentorial intracerebral hemorrhage. J Clin Neurosci 2018;50:208-13.

Intracerebral hemorrhage (ICH) is a devastating disease with high mortality and morbidity rates. In most of the cases, the ICH is evacuated by either a craniotomy (CR) or a decompressive craniectomy (DC), although its optimal treatment has not been established as yet. The objective of this study was to compare the clinical outcomes of patients with spontaneous ICH between the CR and DC groups and determine the factors affecting the clinical prognosis in 286 consecutive patients with a supratentorial large ICH. A CR was performed in 139 patients while a DC was performed in 125 patients. There were no significant difference in the 30-day mortality between the CR group and the DC group (13.7% vs 15.2%). However, the 12-month functional survival was 46% in the CR group, which was significantly higher than that (32%) of the DC group. This suggests a better functional outcome in selected large ICH patients who have undergone a CR rather than a DC.

Contributed by Dr. Mazda K. Turel

Bonati LH, et al. Restenosis and risk of stroke after stenting or endarterectomy for symptomatic carotid stenosis in the International Carotid Stenting Study (ICSS): Secondary analysis of a randomised trial. Lancet Neurol 2018;17:587-96.

The authors aimed to compare the long-term risk of restenosis with stenting or endarterectomy and also to determine if the development of restenosis caused stroke. Patients aged 40 years or older with symptomatic carotid stenosis measuring 50% or more were randomly assigned to either the stenting or the endarterectomy arms in a 1:1 ratio. 1530 individuals were followed up with an ultrasound evaluation (with 737 assigned to stenting and 793 to endarterectomy) for a median period of 4 years. A moderate degree of restenosis (≥50%) occurred in 40% patients after the stenting and in 30% of patients after the endarterectomy. These patients had a higher risk of ipsilateral stroke than did individuals without restenosis in the overall patient population. No difference was noted in the risk of severe restenosis (≥70%) or subsequent stroke between the two treatment groups. Whether or not the restenosis-mediated risk of stroke differs between the stenting and the endarterectomy groups requires further research.

Contributed by Dr. Mazda K. Turel

Zhu C, et al. Therapeutic effect of intensive glycemic control therapy in patients with traumatic brain injury: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2018;97:e11671.

Hyperglycemia is associated with dismal outcomes in patients with traumatic brain injury (TBI). In this study, a systematic review and meta-analysis of the published randomized controlled trials (RCTs) was performed to assess the safety and efficacy of intensive glycemic control (IGC) versus the conventional glycemic control (CGC) for patients following TBI. A total of 7 RCTs involving 1013 cases were enrolled in this study, and the results indicated no significant difference in the 6-month mortality. Subsequently, the IGC was associated with a better neurological outcome, a lower infection rate and a shorter stay in the intensive care unit. However, the IGC therapy can also remarkably increase the risk of hypoglycemia, but it will not affect the mortality in TBI patients.

Contributed by Dr. Mazda K. Turel

Morton RP, et al. Timing of cranioplasty: A 10.75-year single-center analysis of 754 patients. J Neurosurg 2018;128:1648-52.

The authors here present the largest study to date on the complications that develop after the performance of a cranioplasty, focusing specifically on the relationship between the development of complications and the timing of the operation. Over the course of 10.75 years, 754 cranioplasties were performed at a single institution. The 30-day mortality rate was 0.3%. Overall, 25% percent of the patients experienced at least 1 complication including infection necessitating explantation of the flap (6%), postoperative hydrocephalus requiring a shunt (9%), resorption of the flap requiring a synthetic cranioplasty (6%), seizure (4%), postoperative hematoma requiring evacuation (2%), etc., The rate of infection was significantly higher if the cranioplasty had been performed <14 days after the initial craniectomy. Hydrocephalus was significantly correlated with the time to performance of the cranioplasty and was most common in patients whose cranioplasty had been performed <90 days after the initial craniectomy. New-onset seizure, however, only occurred in patients who had undergone their cranioplasty >90 days after the initial craniectomy. Bone flap resorption was least likely when the cranioplasty had been performed between 15 and 30 days after the initial craniectomy. Thus, a cranioplasty performed between 15 and 30 days after the initial craniectomy may minimize infection, seizure, and bone flap resorption, whereas waiting for >90 days may minimize hydrocephalus but may increase the risk of seizure.

Contributed by Dr. Mazda K. Turel

Deer T, et al. Success using neuromodulation with BURST (SUNBURST) study: Results from a prospective, randomized controlled trial using a novel burst waveform. Neuromodulation 2018;21:56-66.

The purpose of the multicenter, randomized, unblinded, crossover ‘Success Using Neuromodulation with BURST (SUNBURST)’ study was to determine the safety and efficacy of a device delivering both a traditional tonic stimulation and burst stimulation to patients with chronic pain of the trunk and/or limbs. Following a successful tonic trial, 100 subjects were randomized to receive one stimulation mode for the first 12 weeks, and then the other stimulation mode for the next 12 weeks. The primary endpoint assessed the noninferiority of the within-subject difference between the tonic and burst stimulation for the mean daily overall visual analog scale score. The study demonstrated that burst stimulation was noninferior to tonic stimulation. The superiority of the burst stimulation was also achieved. Significantly more subjects (70%) preferred burst stimulation over tonic stimulation. This preference was sustained through one year: 68% of subjects preferred burst stimulation, 24% of subjects preferred tonic stimulation, and 8% of subjects had no preference. No unanticipated adverse events were reported and the safety profile was similar to the other spinal cord stimulation studies.

Contributed by Dr. Mazda K. Turel.

Colello RJ, et al. Making football safer: Assessing the current National Football League policy on the type of helmets allowed on the playing field. J Neurotrauma 2018;35:1213-23.

Contact sports such as American style football exposes its players to a significantly high risk of concussion and more severe injuries. After realizing the magnitude of the problem and the long-term consequences, the National Football League (NFL) introduced better-designed helmets and rules to change the game and to prevent repeated injuries. The NFL evaluated the helmets on the “STAR Evaluation System”. The helmet safety rating system is based on the scale of 1-5 determined by the force transmitted to the head in a drop anvil test; the study promoted the helmets with at least a 4-rating to prevent head injuries. Surprisingly, the rule was not mandatory, and the players were still allowed to wear a helmet of their choice and design. Players were well aware of the new policy, and there was a striking difference in the choice of helmet depending on the basis of their location in the field and the style of the game (offense or defense). Older players were more likely to use helmets with lower safety ratings. NFL also evaluated the linear force transmitted with the helmet-to-helmet impaction test, which more closely resembled the on-field realistic impacts. Following the ‘once bitten twice shy’ policy, the players who had earlier suffered from an on-field injury were more compliant with the better helmet designs.

It has earlier been realized that the drop/anvil test fails to recognize and imitate the real impact situation on the field. The projectile test/air cannon test is a better test that replicates the real impact situation. The authors wonder why the projectile test not preferred to the anvil test in the evaluation of the helmet safety. This study highlights another psyche of a player. A professional player has several obligations on himself. He needs to maintain an on-field charisma, he has to be hard on his opponents, the clubs/sponsors demand him to be fierce, and his career is quite short. Despite acknowledging the fact that repetitive traumatic encephalopathy leads to cerebrovascular reactivity alterations, abnormal white matter integrity, and alterations in brain metabolism, players are ready to subject themselves to the risk of injury. The policy makers should be firm in mandatorily ensuring the players'compliance with the high rating helmets, as it is the simplest and probably the most effective measure in preventing the occurrence of concussions. Similar studies are warranted for craniofacial injuries in the world of cricket and in other contact sports.

Contributed by Dr. Manjul Tripathi

Rickard CM, et al. Dressings and securements for the prevention of peripheral intravenous catheter failure in adults (SAVE): A pragmatic, randomised controlled, superiority trial. Lancet 2018;392:419-30.

The very basic first step in the management of an inpatient is securing a peripheral venous access (PVA) for the administration of fluids and medicine. A peripheral cannula is a simple engineering tool with a tremendous responsibility. Perhaps the more daunting task is to maintain that line for a desired duration of time. Repeated lines in different peripheral veins cause significant discomfort to the patient, sometimes at the cost of thrombophlebitis. Looking at the number of these procedures required, there is a huge economic burden too. In this pragmatic analysis, Rickard et al., have compared different dressing materials for the prevention of peripheral line failure. Surprisingly, there was no difference between a simple polyurethane dressings and the other so-called sophisticated dressing materials. It is said that the current research has concentrated on the more sophisticated studies with performance of genetic analyses, and the inclusion of costly implants but this basic treatment step has been neglected so far. One factor still not discussed in the study is the use of intermittent heparinized saline flush to maintain the longevity of the PVA, which can be considered in further studies.

Contributed by Dr. Manjul Tripathi

Serizawa T, et al. Comparison of treatment results between 3- and 2- stage Gamma knife radiosurgery for large brain metastases: A retrospective multi-institutional study. J Neurosurg 2018;7:1-11.

A combination of the availability of health insurance, an earlier detection of tumors, and a better control of the primary pathology has given rise to a better modern day control of intracranial metastases but without much significant improvement in the overall survival. This article has highlighted the comparative efficacy of the third versus the second stage gamma knife radiosurgery (GKRS) for a large volume of brain metastases (BM). There are multiple problems with such treatment schemes, a. A linear quadratic model is not applicable for dose fractionation in such high doses, and hence, the dosing schedule is not standardized; b. how much volume should be treated is not certain; c. what should be the interval between the two treatment sessions has not been established; and d. what should be the sequence when concurrent chemotherapy is also being administered is nebulous. This analysis was commissioned for two reasons: (a) The patient comfort in two stages is more than that seen in the three stages; and, (b) the economic burden is less as the insurance companies do not provide support for multiple admissions. This review (the JLGK1601 study) has proven that the three-staged GKRS is not superior to the two-staged GKRS with regard to the overall survival, tumor progression, neurological deterioration, neurological death, or radiation-related adverse events. Hence, for newly diagnosed, large, especially unresectable brain metastases, with a cumulative tumor volume of up to 50 cc, a two-staged dose fractionated GKRS is an effective treatment modality with comparable results. Such studies are needed in the long term for designing uniform fractionated treatment plans while ensuring patient safety and efficacy.

Contributed by Dr. Manjul Tripathi

Madsen T, et al. Association between traumatic brain injury and risk of suicide. JAMA Neurol 2018;320:580-8.

A severe traumatic brain injury to a person is a turning point in the life of the patient himself and the family members. Though we observe a huge shift in the health care of these patients and improvement by following the Brain Trauma Foundation Guidelines, a lot still needs to be done. Prominent traumatic brain injury (TBI) trials such as the Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUE-ICP) trial have shown that with aggressive measures, we can decrease the mortality, while the morbidity remains the same with the only increase being in the number of patients that remain in a persistently vegetative status. This study is actually an extension in this regard as patients with TBI are at a statistically much higher risk of psychiatric disturbances and suicidal ideation. Patients with TBI, especially those who have sustained a severe and moderate injury, are at a more than three to four times higher risk of suicide than the general population. These patients need better vocational and psychological rehabilitation with frequent societal support to assimilate them in the mainstream society. Management is never over with the discharge of these patients from the hospital.

Contributed by Dr. Manjul Tripathi

Lee CY, et al. Radiation induced secondary tumors for pediatric central nervous system tumors. Experiences of a single institute in Taiwan. Int J Radiat Oncol Biol Phys. 2018;101:1243-52.

This follow up series of 1697 pediatric patients who received radiotherapy for various central nervous system (CNS) malignancies highlights several important concerns with no practical solutions in sight. They observed that chances of secondary malignancies (which are potentially fatal) are statistically higher in children with less than seven years of age, who have undergone craniospinal irradiation, and have received a two-dimensional (2D) irradiation therapy. The secondary tumors were mainly meningiomas, sarcomas, and high-grade gliomas. A medulloblastoma was the most common primary brain tumor that may occur. Surprisingly, all the secondary tumors were in the cranial location and none were in the spinal compartment. The explanation for this observation is a higher radiation dosage being administered to the patients receiving craniospinal irradiation (especially the cranial part) than in the other cohorts. Surprisingly, the pattern of radiation did not affect the prognosis or the chances of development of secondary malignancies, but the numbers suggest much lower chances for the development of a malignancy after the intensity-modulated radiation therapy (IMRT) than the 2D irradiation. Till now, the late failure of the primary CNS tumor is the most common cause of mortality in children with these tumors. Though this case series highlights the long-term late complications of therapeutic irradiation, the solutions are not in sight. Probably, genetic profiling and dose de-escalation might help in reducing the chances of development of secondary malignancies.

Contributed by Dr. Manjul Tripathi

Hu S, et al. A meta-analysis of risk factors for the formation of de novo intracranial aneurysms. Neurosurgery 2018. doi: 10.1093/neuros/nyy332.

A case of aneurysmal SAH needs to be followed on a long term basis even after successful management of the initial bleed. This is because of the risk of development of de novo aneurysms, that is, aneurysms developing at a location distinct from the original aneurysm. Though the prevalence of de novo aneurysms is less, their rupture rate is much higher. The authors included 14 studies with 6389 patients having 197 de novo aneurysms. The main risk factors that were responsible for the development of de novo aneurysms were the female gender, a younger age (<40 years), a history of smoking, the presence of multiple saccular intracranial aneurysms at the first instance, and the presence of initial aneurysm on the internal carotid artery angiogram. Thus, the findings of this study may be utilized in the patient and family education, by stressing on the need for lifestyle modification as well as on the essentiality of regularly following-up these patients.

Contributed by Dr. Ashish Aggarwal and Dr. Anant Mehrotra

Can A, et al. Low serum calcium and magnesium levels and rupture of intracranial aneurysms. Stroke 2018;49:1747-50.

The authors of the present study have tried to correlate the levels of serum calcium and magnesium and the risk of intracranial aneurysm rupture. A total of 1275 patients were included in the study. Amongst them, there were a total of 1704 aneurysms of which 900 had ruptured. The patients with ruptured aneurysms were taken as cases and the patients with unruptured aneurysms were taken as controls. Serum calcium and magnesium (albumin corrected) levels were noted in all the patients. The study found out that patients with (albumin corrected) hypocalcemia and hypomagnesemia were significantly more frequently diagnosed with a ruptured aneurysm. This has been attributed to two possible mechanisms: The low calcium and magnesium levels can lead to a disturbances of the coagulation pathway that may enhance the risk of rupture; and, the hypocalcemia induced changes in the vascular reactivity may lead to the development of hypertension.

Contributed by Dr. Ashish Aggarwal

Buerba RA, et al. Bisphosphonate and teriparatide use in thoracolumbar spinal fusion: A systematic review and meta-analysis of comparative studies. Spine (Phila Pa 1976). 2018;43:1014-23.

In patients with osteoporosis and poor bone quality, there are chances of implant failure after spinal instrumentation. Hence, spinal surgeons prefer to prescribe medications for treatment of osteoporosis as an adjunct in spinal fusion surgery. In this systematic review and meta-analysis, the authors have compared the use of bisphosphonates and teriparatide (recombinant parathyroid hormone) on various radiographic and functional outcomes after thoracolumbar spinal fusion in patients of degenerative lumbar spine diseases and in patients undergoing treatment for adult spinal deformity with osteoporosis. They included nine studies comprising a total of 536 patients. The fusion and the screw loosening rates were not statistically different in the bisphosphonate group when compared to the controls. Cage subsidence and vertebral fractures rates were, however, lower in the bisphosphonate group. Fusion rates were higher in the teriparatide group versus the tisphosphonate group.

Contributed by Dr. Ashish Aggarwal

Kipnis J. The Seventh sense. Sci Am 2018;319:28-35.

This article might change the way we perceive the role of immune system in the central nervous system (CNS) health and disease. The conventional medical school teaching had been that there is an absence of lymphatic system in the brain and there is rarely any interaction between the CNS and the immune system. There is also a belief that the robust blood brain barrier system makes sure that the absence of a lymphatic system does not make any meaningful difference. By quoting various experiments, the author has shown the occurrence of a paradigm shift on how we view the interactions of the brain and the immune system. In a mice experiment, the development of amyotrophic lateral sclerosis and Alzheimer's disease was more severe and rapid after the experimental stunning of the immune response. Behavioural experiments in mice revealed that the ones lacking an adaptive immunity performed poorly in the domains of spatial learning and memory. While trying to locate the source of the immune system, the author found that meninges contain the immune cells and lymphatic vessels. Further, cytokines produced by immune cells from the meninges can interact with the neurons in the prefrontal cortex. We have got five special senses—sight, hearing, taste, smell and touch. In addition, a sixth sense is the sense of proprioception. These senses continuously update the body for any changes in the external and the internal environments. Due to the suspected close association of the immune system to the brain, the author proposes it as the seventh sense. So, what are the clinical implications? In future, targeting the immune system may have desirable effects on many CNS diseases.

Contributed by Dr. Ashish Aggarwal

Bayerl SH, et al. Two-level cervical corpectomy – Long term follow up reveals the high rate of material failure in patients, who received an anterior approach only. Neurosurg Rev 2018. Doi: 10.1007/s10143-018-0993-6.

The authors, in this paper, have compared anterior fixation only with both anterior and posterior fixation (circumferential fusion) after a two–level cervical corpectomy. The indications for surgery were cervical spondylotic myelopathy, tumours and infections. Although patients in both the groups improved with respect to pain and myelopathic features, implant failure and the rate of revision surgery were more in the anterior group (33% vs 0%) after a 30-month follow up period. Their data clearly shows the advantage of providing an additional posterior fixation to the anterior construct after two-level cervical corpectomy surgeries, and thus, they have recommended a routine 360 fusion for such cases.

Contributed by Dr. Navneet Singla

Mak SK, et al. Recovery of oculomotor nerve palsy after endovascular and surgical treatment of posterior communicating aneurysms: A single institutional experience. Asian J Neurosurg 2018;13:555-9.

This retrospective review compares the rate of recovery of third cranial nerve after treatment of posterior communicating artery aneurysm. A total of 22 such patients, out of which 13 had unruptured and 9 had ruptured aneurysms, were taken up for this analysis. 59% had complete oculomotor nerve palsy (ONP) while the affection was partial in the remaining patients. 11 patients each underwent clipping of the aneurysm or endovascular coiling. Within one week, 45% of the patients of surgical group achieved complete ONP recovery as compared to 0% in coiling group. At one month, the rate of recovery was 63.6% vs 18.2%, and at one year, 100% vs 72.7%. Patients with partial ONP at presentation recovered faster as compared to those with complete ONP. The difference in the rate of recovery in the surgical and endovascular groups was more pronounced in ruptured aneurysms. Thus, surgery resulted in a faster and more complete recovery of ONP due to the presence of a posterior communicating artery aneurysm as compared to endovascular coiling.

Contributed by Dr. Navneet Singla

Zhe Z, et al. The correlation between gene polymorphisms of endothelial nitric oxide synthase and aneurysmal subarachnoid hemorrhage. Neurosurg Rev 2018. doi: 10.1007/s10143-018-0992-7.

Endothelial nitric oxide synthase (eNOS) is an important endothelial regulator helping in the regulation of vasodilatation, protection of endothelial cells and maintenance of the vascular wall integrity. The authors have studied the association of polymorphisms of eNOS- T786C on the promoter region, and of G894T on the coding region, with the occurrence and prognosis of aneurysmal subarachnoid haemorrhage (aSAH).169 patients of aSAH were taken as cases and 156 healthy individuals as controls. A significant difference was found in the distribution of T786C and G894T genotype and allele frequency between cases and controls, the CC genotype of T786C, and the TT genotype of G894T being significantly higher in the cases. It indicates a higher risk of aSAH in the 786C and 894T alleles of eNOS. There was also a significant difference in the distribution of allele frequency of G894T and T786C and genotype of G894T among the good (GOS 4-5) and bad prognosis patients (GOS1-3). On multivariate logistic regression, hypertension and T786C and G894T polymorphism of eNOS were found to be independent risk factors for the occurrence of aSAH. Hypertension, a higher Hunt and Hess grade and G894T polymorphism had a higher risk of an adverse clinical outcome.

Contributed by Dr. Navneet Singla

Nasi D, et al. Risk factors for post-traumatic hydrocephalus following decompressive craniectomy. Acta Neurochir 2018;160:1691–8.

Post traumatic hydrocephalus (PTH) develops in a significant number of patients who undergo decompressive craniectomy (DC) for traumatic brain injury (TBI). It may be the result of converting a closed box of cranial cavity into an open box after a DC. 190 patients were included in this study, who underwent DC for TBI and were followed up for the development of PTH. At 30 days of DC, 130 patients were alive, out of which 37 (28.4%) developed PTH. 34 patients underwent a ventriculoperitoneal shunt for the treatment of PTH. On univariate analysis, a young age, the presence of SAH, bifrontal decompression, the presence of an inter-hemispheric hygroma and delayed cranial reconstruction were found to be risk factors for PTH, but on multivariate analysis, only the development of a hygroma and a delayed cranioplasty were significantly associated with the need for a ventriculoperitoneal shunt. Development of PTH resulted in a significantly poor outcome in the survivors.

Contributed by Dr. Navneet Singla

Budohoski KP, et al. Predictors of early progression of surgically treated atypical meningiomas. Acta Neurochir 2018;160:1813–22.

Atypical meningiomas represent a heterogenous group with a variable clinical behaviour and there are no uniform management guidelines available at the moment. 220 patients diagnosed with an atypical meningioma (World Health Organisation grade 2) on histology were analysed in this study. Gross total surgical excision was achieved in 143 of these patients. Adjuvant radiotherapy was given in 57 (26%) patients. Subtotal resection, parasagittal location, peritumoural oedema and a mitotic index >7/10 high power field were significantly associated with an early recurrence. Adjuvant radiotherapy resulted in lower rates of early recurrence (within 2 years). Interestingly, brain invasion was not found to be associated with an early recurrence in this study. The authors recommend that identification of clinical, biological and molecular predictors of recurrence are required to stratify the management decisions in atypical meningiomas.

Contributed by Dr. Navneet Singla

Tayebi MA, et al. Modern radiosurgical and endovascular classification schemes for brain arteriovenous malformations. Neurosurg Rev 2018. doi: 10.1007/s10143-018-0983-8.

Brain arteriovenous malformations require a multidisciplinary approach comprising of 3 principal treatments either in isolation or in combination – microsurgical excision, stereotactic radiosurgery (SRS) and endovascular obliteration. For appropriate management, a sound classification system is required for a proper case selection and for predicting an expected outcome. The Spetzler-Martin grading and its modifications are very well established for its microsurgical management but the same does not always hold true for the other two treatment options, i.e., SRS and endovascular management. Various grading systems used for SRS are: Symptomatic post-radiosurgery injury expression (SPIE) scale (2000), Pittsburgh radiosurgery-based AVM scale (RBAS) and its modifications (2002–2008), Heidelberg score (2012), Virginia radiosurgery AVM scale (2013), Proton-beam SRS (PSRS) AVM score (2014). Of these, the modified-RBAS and PSRS have been found to be most accurate systems for prediction of outcome after SRS. The classification systems used for endovascular obliteration are: Viñuela-Guglielmi grading system (1995), Sheikh et al. grading system (2000), Toronto score (2001), Puerto Rico grading scale (2010), Buffalo score (2015), AVM embocure score (AVMES) (2015), and Rothschild-Montreal grading scale for deep AVMs (2017). However, none of the proposed grading systems for endovascular management have gained widespread popularity. The author calls for a need of a comprehensive classification system and the inclusion of genetic and molecular factors in the future grading systems.

Contributed by Dr. Ashish Aggarwal

Dekker L, et al. Importance of reperfusion status after intra-arterial thrombectomy for prediction of outcome in anterior circulation large vessel stroke. Interv Neurol 2018;7:137-47.

Quick and complete reperfusion of the occluded vessel is the ultimate goal of stroke therapy which governs the eventual clinical outcome. The authors aimed at deciphering the association between successful reperfusion and the clinical outcome in this study. From their prospective stroke registry, clinical, radiological, and procedural variables of patients treated with intra-arterial therapy (IAT) were assessed vis-à-vis the patient's functional outcome at 3 months using the modified Rankin Scale (mRS). The reperfusion status was evaluated with the modified TICI (Thrombolysis In Cerebral Infarction) score, and the eTICI (expanded TICI) score in a total of 119 patients. An age >80 years, the National Institutes of Health Stroke scale (NIHSS) at presentation being >15, and an incomplete reperfusion status were the strongest predictors of a poor outcome. The eTICI score cutoff value of ≥2C improved the predictive value for a good clinical outcome than the score cut-off value of ≥2B, indicating that better the extent of recanalization, better is the clinical outcome.

Contributed by Dr. Chirag K. Ahuja

Larsen N, et al. Vessel wall enhancement in unruptured intracranial aneurysms: An indicator for higher risk of rupture? High-resolution MR imaging and correlated histologic findings. Am J Neuroradiol 2018;39:1617-21.

Predicting the rupture risk in an unruptured aneurysm holds extreme importance considering the attendant mortality and morbidity of such an event. Wall enhancement on high resolution MRI has been shown to be an imaging biomarker of aneurysm instability indicating inflammation and degeneration. The authors compared the intensity of aneurysm wall enhancement in unruptured MCA aneurysms on MR vessel wall imaging, with a histologic analysis (with myeloperoxidase [MPO] and cluster of differentiation (CD) 34 stains) following aneurysmal clipping. Out of 13 aneurysms, 5 showed a strong wall enhancement (4 of these revealed inflammatory cell infiltration on MPO, 3 showed neovascularization and 2 showed the presence of vasa vasorum). Of the rest, 7 aneurysms showed no wall enhancement with 1 having only mild enhancement. None of these bore evidence of inflammatory cell invasion or neovascularization, and they all lacked vasa vasorum. The authors concluded that aneurysm wall enhancement was associated with inflammatory cell invasion, neovascularization, and the presence of vasa vasorum, which can be used for stratification of aneurysms at risk for rupture. These aneurysms could subsequently be offered the aneurysm obliteration therapy in a timely fashion.

Contributed by Dr. Chirag K Ahuja

Pelizzari L, et al. Five-year longitudinal study of neck vessel cross-sectional area in multiple sclerosis. Am J Neuroradiol 2018;39:1703-9.

The etiology of multiple sclerosis (MS) has long been a matter of debate. One proposed theory incriminates vascular contribution to the disease with alterations of neck vessel cross-sectional area shown in some studies. The present study investigated the evolution of the neck vessel cross-sectional area in patients with MS and in healthy controls during a 5-year follow-up period. 69 MS patients (44 relapsing-remitting MS, 25 progressive MS) and 22 appropriately matched healthy controls were examined 5 years apart using neck MR angiography. Cross-sectional areas (CSA) were computed for the common carotid (CC)/internal carotid (IC) arteries, vertebral arteries, and internal jugular veins (IJVs) from C3 to C7 cervical levels. Longitudinal CSA differences were tested within the study groups and between patients with MS with and without cardiovascular disease. No significant CSA differences were seen between patients with MS and healthy controls at baseline or at follow-up. However, the follow-up showed a significant CSA decrease in patients with MS for the CC, IC and vertebral arteries and also for the IJVs. Patients with MS without cardiovascular disease had significantly greater changes than patients with MS with cardiovascular disease for the internal jugular veins at all levels. It was concluded that patients with MS showed significant CSA decrease of all major neck vessels, regardless of the disease course and cardiovascular status.

Contributed by Dr. Chirag K. Ahuja

Cagnazzo F, et al. Acutely ruptured intracranial aneurysms treated with flow-diverter stents: A systematic review and meta-analysis. Am J Neuroradiol 2018;39:1669-75.

The role of flow-diverter stents in ruptured aneurysms has been debatable due to the associated inherent delay in aneurysmal occlusion. The authors conducted a meta-analysis of 8-year data in medical literature comprising of 20 studies constituting 223 patients who underwent flow diversion for ruptured intracranial aneurysms. The following variables were analysed - aneurysm occlusion rate, complications, re-bleeding, and factors influencing the studied outcomes. Immediate angiographic occlusion was obtained in 32% aneurysms, whereas the long-term complete/near-complete aneurysm occlusion rate was 88.9%. The treatment-related complication rate was 17.8% with higher complications seen in the posterior circulation and after treatment with multiple stents. Aneurysmal re-bleeding after treatment was low (4%). Thus, it was concluded that the flow-diversion treatment of ruptured intracranial aneurysms yields a high rate of long-term angiographic occlusion with a relatively low rate of aneurysm re-bleeding.

Contributed by Dr. Chirag K. Ahuja

De Meulemeester J, et al. Many randomized clinical trials may not be justified: A cross-sectional analysis of the ethics and science of randomized clinical trials. J Clin Epidemiol 2018;97:20-5.

It has been proposed that justification of randomized clinical trials (RCTs) should be based on three scientific criteria: (1) they should be designed around a clear hypothesis; (2) uncertainty should exist around that hypothesis; and, (3) uncertainty should be established through a systematic review. Based on these criteria, a cross-sectional analysis of all RCTs published in the New England Journal of Medicine and the Journal of the American Medical Association in 2015 were evaluated. Each article and protocol was reviewed for: (1) a clearly stated central hypothesis; (2) references to “equipoise,” or “consensus;” (3) some indication of evidentiary uncertainty; and, (4) a meta-analysis or systematic review surrounding the hypothesis or study question. Out of 208 RCT articles and 199 protocols that were included, 76% had a clearly stated hypothesis, 99% referenced some form of uncertainty, and 54% cited a relevant systematic review or meta-analysis. Only 44% of the combined texts were in accordance with all the three scientific criteria. The authors propose that the scientific criteria for RCTs should be replaced by an expectation that RCTs have a clearly stated, meaningful hypothesis around which uncertainty has been established through a systematic review of the literature.

Contributed by Dr. Chirag K. Ahuja

Bath PM, et al. Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS randomised control trial. Health Technol Assess 2018;22:1-76.

It is well known that two antiplatelet agents are better than one for preventing recurrent stroke after acute ischemic stroke or transient ischemic attack (TIA). On the same tenet, intensive treatment with three agents might seem to be better, provided it does not cause undue bleeding. The authors compared the safety and efficacy of intensive therapy with guideline antiplatelet therapy in these two groups. The participants were randomized to receive 1 month of intensive (combined aspirin, clopidogrel and dipyridamole) or guideline (combined aspirin and dipyridamole, or clopidogrel alone) antiplatelet agents with a 90-day follow-up period. The primary outcome was the incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days. Other outcomes included bleeding, death, myocardial infarction (MI), disability, mood, cognition and quality of life. The trial was prematurely stopped after recruitment of 3096 participants. The incidence and severity of recurrent stroke or TIA did not differ between the two groups; however, the incidence of major bleeding was increased with intensive as compared with guideline therapy, with no differences in the all-cause mortality, or in the composite of death, stroke, MI and major bleeding. The study deduced that the use of three antiplatelet agents was associated with an increased risk of bleeding without any significant reduction in the recurrence of stroke or TIA.

Contributed by Dr. Chirag K. Ahuja

Malhotra K, et al. Top-100 highest-cited original articles in ischemic stroke: A bibliometric analysis. World Neurosurg 2018;111:649-60.

The impact of any research article is proportional to the total number of citations it has received. This article aimed to identify the top-100 articles published on ischemic stroke and to evaluate their characteristics. The authors selected 934 journals that published original articles on ischemic stroke, based on the database of Journal Citation Reports. The top-100 articles, i.e., articles with more than 400 citations were identified based on Web of Science citation search tool. All these articles were published from 1970 to 2015, with the decade of 1990-1999 contributing 47 articles of historical significance. The median figures of the total citations and the annual citations were 625.0 and 35.7, respectively. The majority of the articles belonged to institutes located in the United States (n = 57) and were published in the New England Journal of Medicine or Stroke (n =25 each) journal. The median impact factor for the journals that published the top-100 ischemic stroke citation classics was 9.11. It reiterates that stroke is still one of the leading causes of morbidity and generates a lot of mindful research amongst physicians.

Contributed by Dr. Chirag K. Ahuja

Yao YC, et al. Bracing following transforaminal lumbar interbody fusion is not necessary for patients with degenerative lumbar spine disease: A prospective, randomized trial. Clin Spine Surg: 2018. doi: 10.1097/BSD.0000000000000697.

Bracing following spinal fusion for lumbar degenerative disease is used commonly without any proven benefit. In this prospective randomized trial, the authors aimed to evaluate the outcome of bracing following transforaminal lumbar interbody fusion (TLIF) in patients with degenerative lumbar spine disease. Ninety patients who underwent instrumented TLIF were randomly assigned to the brace group (n = 44, rigid brace for 12 weeks) or no brace group (n = 46, a soft corset for 2 weeks). Visual Analogue Scale and Oswestry Disability Index scores at each follow-up were not significantly different between the 2 groups. The fusion rate and complications at the 12-month postoperative follow-up period were not significantly different between the 2 groups. The authors concluded that in patients with degenerative spinal disease who receive TLIF, wearing a rigid brace postoperatively is unnecessary.

Contributed by Dr. Chirag K. Ahuja

Thompson T et al., Driving impairment and crash risk in Parkinson disease. Neurology 2018. doi: 10.1212/WNL.0000000000006132.

In this meta-analysis, seven major databases were systematically searched for studies comparing patients with Parkinson's disease (PD) to healthy controls (HC) on the overall driving performance to provide the best possible evidence base for guiding driving decisions in patients with PD. Fifty studies comprising 5,410 participants met the study eligibility criteria. The analysis found the odds of on-the-road test failure to be 6.16 times higher and the odds of simulator crash to be 2.63 times higher for patients with PD, with poorer overall driving rating. However, the self-reported real-life crash involvement did not differ between people with PD and HC. The findings remained unchanged after accounting for the differences in age, sex, and driving exposure. No moderating influence of the disease severity was found on the scores. The findings of this meta-analysis provide persuasive evidence for substantial driving impairment in PD patients and highlight the need for objective measures for prevening a crash while driving in these patients.

Contributed by Dr. Aastha Takkar

Ziad A, et al. Anticholinergic drug use and cognitive performances in middle age: Findings from the CONSTANCES cohort. J Neurol Neurosurg Psychiatry 2018. doi: 10.1136/jnnp-2018-318190.

The association between the use of anticholinergic (AC) drugs and cognitive performance in the elderly population has been well observed in the literature. This cross sectional study used baseline data from 34,267 patients [Consultants des centres d'examen de santé de la sécurité sociale (CONSTANCES) cohort] and aimed to assess the relationship between the exposure to AC drugs and cognitive performance in middle-aged adults. Eight classes of AC drugs were differentiated. Validated neuropsychological tests were done for the assessment of memory and executive functions. A negative association between the overall cumulative AC exposure and cognitive performance was noted. The use of drugs with possible AC effect was only found to be affecting executive functions. Across the drug classes, a negative association between the use of AC antipsychotics and all cognitive functions was noted and a heterogeneous association was found with the use of AC anxiolytics, AC opioids and AC drugs targeting the gastrointestinal tract. No significant associations were seen between the use of antihistamines, antidepressants, medications affecting the cardiovascular system or other AC medications and the cognitive function. It was, therefore, concluded that the association between AC drugs and cognitive performance was highly heterogeneous across the drug classes.

Contributed by Dr. Aastha Takkar

Sawada H, et al. Early use of donepezil against psychosis and cognitive decline in Parkinson's disease: A randomized controlled trial for 2 years. J Neurol Neurosurg Psychiatry 2018. doi: 10.1136/jnnp-2018-318107.

This double-blinded, placebo-controlled trial on 145 non- demented PD patients was done to investigate whether or not an early and a long-term use of donepezil prevented the development of psychosis. The primary outcome measure was survival time to psychosis that was predefined by the Parkinson's Psychosis Questionnaire (PPQ). The secondary outcome measures included psychosis development within 48 weeks, the total PPQ score, the mini-mental state examination (MMSE) and the Wechsler memory scale (WMS). Kaplan-Meier curves for psychosis development were very similar between the two groups. The changes in MMSE and WMS-1 (auditory memory) were significantly better with donepezil compared to the placebo. This study has shown that despite its beneficial effects on PPQ, MMSE and auditory WMS score, donepezil had no prophylactic effect on the development of psychosis in PD.

Contributed by Dr. Aastha Takkar

Kosekahya P et al. Optic nerve head elastometry in both eyes of patients with unilateral non-arteritic anterior ischaemic optic neuropathy – may it be a novel aspect of the pathogenesis? Neuro-Ophthalmol 2018. doi: 10.1080/01658107.2017.1397702.

In this prospective, cross sectional study of 30 patients with non-arteritic anterior ischemic optic neuropathy (NA-AION), the biomechanical properties of bilateral optic nerve heads (ONH) and the cornea were investigated. ONH elastometry was measured with real-time elastography, and the corneal elastometry was measured with ocular response analyser. Both the parameters were seen to be lower in both eyes of patients with unilateral non-arteritic ischaemic optic neuropathy than in the healthy control eyes. These biomechanical differences may contribute towards the pathogenesis, risk of development and prognosis of NA-AION and hence warrant further investigations.

Contributed by Dr. Aastha Takkar

Zhang L, et al. Risk of acute ischemic stroke in patients with monocular vision loss of vascular etiology. J Neuro-Ophthalmol. 2018. doi: 10.1097/WNO.0000000000000613.

This retrospective, cross sectional study was carried out in patients with monocular vision loss (MVL) of suspected or confirmed vascular etiology. The patients were included if there were no other focal neurological deficits and if the MRI was done within seven days of onset of the visual symptoms. Out of 641screened patients, 41 were included in the study and the risk of concurrent acute ischemic stroke was assessed. The presence or absence of acute stroke assessed by MRI diffusion-weighted imaging (DWI) was the main study outcome and 19.5% patients were found to have findings on brain MRI positive for acute cortical strokes, even in the absence of other neurologic deficits. There is, hence, a high risk of developing concurrent and silent strokes in patients presenting with only MVL, underscoring the importance of investigating and managing these patients holistically.

Contributed by Dr. Aastha Takkar

Tsivgoulis G, et al. Intravenous thrombolysis for ischemic stroke patients on dual antiplatelets. Ann Neurol 2018;84:89-97.

There are reports in the literature which suggest that patients who are on dual antiplatelet therapy prior to receiving intravenous thrombolysis have increased chances of developing intracerebral haemorrhage. The authors of this observational retrospective study performed a subgroup analysis of Safe Implementation of Treatment in Stroke (SITS) database. Using propensity matched scoring, the authors found comparable rates of symptomatic intracerebral haemorrhage, 3 months functional outcome and 3 months mortality rates between the patients on dual antiplatelet therapy and the controls. This study further supports the recent American Stroke Association Guidelines that the benefit of intravenous thrombolysis in patients receiving dual antiplatelet therapy outweighs the risk of developing symptomatic intracerebral haemorrhage. Thus, the prior use of dual antiplatelet therapy should not be taken as a contraindication to intravenous thrombolysis.

Contributed by Dr. Sahil Mehta

Tetz G, et al. Parkinson's disease and bacteriophages as its overlooked contributors. Sci Rep 2018;8:10812.

Recent and upcoming literature highlights the role of gut microbiota in the pathogenesis of Parkinson's disease. Alterations in gut microbiota lead to deposition of misfolded alpha synuclein in the enteric nervous system, which is then propagated to the central nervous system. The authors of this report studied the role of bacteriophages and phagobiota in influencing the development of Parkinson's disease. They performed a metagenomic analysis of the intestinal phagobiota in parkinsonian and non-parkinsonian individuals. The authors found that patients with Parkinson's disease exhibited reduction in the lactic acid producing bacteria, especially the Lactococcus species involved in the dopamine production and intestinal permeability, due to an increase in the lytic c2- like and 936-like lactococcal phages present frequently in the dairy products. This study highlights that gut phagobiota may both have diagnostic and therapeutic implications in Parkinson's disease.

Contributed by Dr. Sahil Mehta

Fridriksson J, et al. Transcranial direct current stimulation vs sham stimulation to treat aphasia after stroke: A randomized clinical trial. JAMA Neurol. 2018. doi: 10.1001/jamaneurol.2018.2287.

Aphasia is a debilitating speech disorder for which no effective treatment exists and speech therapy remains the only treatment option as of now. The authors of this double-blinded randomized controlled trial tested the utility of studying anodal transcranial direct current stimulation (a-TDC) in addition to speech therapy for post stroke aphasias. 79 patients with >6 months post-stroke aphasia were enrolled in the outpatient clinic and the primary outcome was improvement in the naming ability. The authors found a 70% increase in the naming ability following TDC stimulation compared to sham stimulation. Further randomized controlled trials with a large sample size should be studied to assess its efficacy and feasibility.

Contributed by Dr. Sahil Mehta

Gaziano JM, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): A randomised, double- blind, placebo-controlled trial. Lancet 2018. doi: 10.1016/S0140-6736(18)31924-X.

The use of aspirin for the primary prevention of cardiovascular disease is controversial. Previous studies highlight the importance of aspirin in preventing myocardial infarction but not stroke. The authors of this multicentre randomized double blinded placebo controlled trial assessed the safety and efficacy of enteric coated aspirin (100 mg/day) compared to a placebo in the prevention of cardiovascular events in patients with moderate risk of cardiovascular disease (based on the presence of dyslipidaemia, hypertension and excluding diabetes mellitus). They found that aspirin did not lower the risk of major cardiovascular events and stroke at 60 months. Gastrointestinal bleeding, though mild, occurred more frequently in the aspirin group compared to the placebo group. There was no difference in the incidence of fatal events. Thus, the overall decision to use aspirin should still be based on the physician- patient discussion.

Contributed by Dr. Sahil Mehta

Batla A, et al. Young- onset multiple system atrophy: Clinical and pathological features. Mov Disord 2018;33:1099-1107.

The onset of multiple system atrophy (MSA) before the age of 40 years is referred to as young-onset MSA (YOMSA). It accounts for less than 1% of MSA patients. The authors reported the clinical features in 22 patients with young onset MSA (8 with pathologically confirmed disease) and compared them with 16 pathologically confirmed young onset PD (YOPD) patients and late onset MSA (LOMSA) patients. The mean age of onset was 36.7 years; 20 were of the parkinsonian type and 2 of the cerebellar type. Myoclonic tremor, dystonia and pyramidal signs were significantly more common in the young onset MSA patients compared to the young onset PD and the late onset MSA patients. Levodopa induced dyskinesias occurred more commonly in the YOPD patients. YOMSA patients had orofacial dyskinesia with 83% response rate to levodopa. The authors concluded that the presence of rest tremor or levodopa responsiveness cannot exclude the possibility of YOMSA. Further studies involving larger patient numbers are required to confirm these observations.

Contributed by Dr. Sahil Mehta

Pai FY, et al. Low-dose gamma knife radiosurgery for acromegaly. Neurosurgery. 2018. doi: 10.1093/neuros/nyy410.

The usual recommended dose of gamma knife radiosurgery (GKS) in patients with acromegaly is ≥ 25 Gy. However, it is not always possible to deliver this high dosage due to the proximity of the optic apparatus. This single centre retrospective study aimed to evaluate the efficacy and safety of low-dose (<25 Gy) GKRS in the treatment of patients with acromegaly. The median margin dose, the isodose line, and the treatment volume were 15.8 Gy, 57.5%, and 4.8 mL, respectively, in their 76 patients. Radiation dose to the optic apparatus was limited to 10 Gy. Biochemical remission was achieved in 43.4% of patients. Actuarial remission rates were 20.3%, 49.9%, and 76.3% at 4, 8, and 12 years, respectively. Absence of cavernous sinus invasion (P = 0.042) and lower baseline insulin-like growth factor-1 levels (P = 0.019) were significant predictors of remission. New hormonal deficiencies were found in 9 (11.8%) patients. Actuarial hormone deficiency rates were 3%, 14%, and 22.2% at 4, 8, and 10 years, respectively. Two (2.6%) patients experienced a recurrence after the initial remission. No optic complications were encountered. The authors concluded that remission rates comparable to those with standard GKRS margin doses can be achieved with low dosage GKRS in acromegalic patients.

Contributed by Dr. Kanwaljeet Garg

Yoshii T, et al. A prospective comparative study in skin antiseptic solutions for posterior spine surgeries: Chlorhexidine-gluconate ethanol versus povidone-iodine. Clin Spine Surg 2018;31:353-6.

Chlorhexidine-gluconate (CHG) and povidone-iodine (PD-I) are the two common antiseptic solutions used in spine surgeries. Some earlier studies have shown that CHG is more effective for skin antisepsis than PD-I in joint surgeries. However, there is no data from spine surgery patients. This prospective comparative study aimed to compare the efficacy of these two standard antiseptic solutions in eliminating bacterial pathogens from surgical sites in posterior spine surgeries. A total of 190 patients who underwent posterior spine surgeries were included in this study (98 in 0.5% CHG group and 92 in 10% PV group). Sterile culture swabs were used to obtain samples from the skin area adjacent to the planned incision site before preparation, after preparation, and after wound closure. Before and after the skin preparation, there were no significant differences observed in the culture positive rate between the two groups. The culture positive rate after wound closure in the CHG- treated group (5.1%) was lesser than in the PD-I-treated group (14.1%) [P = 0.046]. However, no difference was found in the infection rates between the 2 groups. The authors concluded that while both CHG-ethanol and PD-I were equally effective at eliminating the bacterial flora from the surgical site, CHG-ethanol showed a more favorable long-lasting effect on the skin antisepsis in the posterior approaches to the spine.

Contributed by Dr. Kanwaljeet Garg

Sandström L, et al. Unilateral left deep brain stimulation of the caudal zona incerta is equally effective on voice tremor as bilateral stimulation: Evidence from 7 patients with essential tremor. Stereotact Funct Neurosurg 2018;96:157-61.

Response of voice tremor to deep brain stimulation (DBS) is considered to be inferior than the response of arm tremor in essential tremor patients. Moreover, bilateral DBS is considered to be better than unilateral DBS in these patients. The authors evaluated the efficacy of unilateral DBS targeted at the caudal zona incerta (cZi) in relieving voice tremor. They evaluated seven patients with voice tremor off stimulation during bilateral stimulation using their clinical settings, and during unilateral left stimulation during their repetitions with increasing stimulation amplitude. The authors found that the effect on voice tremor was comparable or better in the 6 patients with unilateral left stimulation compared to bilateral stimulation. The seventh patient required a slightly higher amplitude to achieve similar results with unilateral DBS as compared to bilateral DBS. The authors concluded that unilateral left and bilateral cZi-DBS had comparable effects on voice tremor.

Contributed by Dr. Kanwaljeet Garg

Khechen B, et al. Comparison of postoperative outcomes between primary MIS TLIF and MIS TLIF as a revision procedure to primary decompression. Spine (Phila Pa 1976) 2018. doi: 10.1097/BRS.0000000000002759.

Minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) and lumbar decompression (LD) are commonly used in lumbar degenerative disease. However, a few patients require TLIF after LD due to recurrent/persistent symptoms. A few studies have reported the differences in the outcomes between patients undergoing MIS TLIF as a primary procedure and those undergoing MIS TLIF following primary LD. The objective of this study was to compare the percentage of postoperative improvement in surgical- and patient- reported outcomes (PROs) between patients undergoing primary MIS TLIF and MIS TLIF following primary LD. Fifty-two patients were selected from a prospectively- maintained database with 26 patients in each group. There were no differences in the baseline or perioperative variables. Revision and primary MIS TLIF patients experienced similar improvements in PROs at all the postoperative time points. The authors concluded that a primary decompression does not compromise clinical outcomes in patients undergoing MIS TLIF later. As such, patients should not be precluded from undergoing MIS TLIF based on the history of a previous lumbar decompression.

Contributed by Dr. Kanwaljeet Garg

Ko AL, et al. Asleep deep brain stimulation reduces the incidence of intracranial air during electrode implantation. Stereotact Funct Neurosurg 2018;96:83-90.

Microelectrode recording (MER) is done in awake deep brain stimulation (wkDBS), while in asleep DBS (aDBS), image guided implantation is done rather than MER. Apart from patient comfort, other advantages of aDBS include a shorter operative time and less cerebrospinal fluid egress. This may, in turn, decrease the incidence of pneumocephalus, which in turn may reduce the brain shift during implantation. Large volumes of intracranial air have been correlated with shifting of brain structures during the DBS procedure, a variable that could impact the accuracy of electrode placement. The authors compared the incidence and volume of pneumocephalus during awake (wkDBS) and aDBS procedures. They retrospectively reviewed all cases of bilateral DBS performed at their centre. Pneumocephalus was noted in 66% of wkDBS and 15.6% of aDBS. The average volume of air was significantly higher in wkDBS than aDBS (8.0 vs. 1.8 mL). Volumes of air greater than 7 mL, which have previously been linked to brain shift, occurred significantly more frequently in wkDBS than aDBS (34 vs 5.6%). wkDBS resulted in significantly larger cortical brain shifts (5.8 vs. 1.2 mm). The authors concluded that aDBS reduces the incidence of intracranial air, is associated with lesser air volumes, and with lesser cortical brain shift.

Contributed by Dr. Kanwaljeet Garg

Meng Y, et al. The impact of the difference in O-C2 angle in the development of dysphagia after occipitocervical fusion: A simulation study in normal volunteers combined with a case-control study. Spine J 2018. pii: S1529-9430(18)30007-X.

Dysphagia is one of the serious complications after an occipito-cervical fusion (OCF), and the difference between postoperative and preoperative O-C2 angle (dO-C2A) has been proposed to be an indicator in predicting the occurrence of this complication. The aim of this simulation study combined with a retrospective case-control study was to explore the threshold of dO-C2A between dysphagia and normal swallowing by a simulation study; and, to evaluate the validity of the threshold of dO-C2A in predicting dysphagia after OCF via a case-control study. First, in the simulation study, two lateral x-rays of the cervical spine were done in neutral position and dysphagia position in 30 volunteers. The cumulative frequency diagram of dO-C2A in the dysphagia position was analysed to identify the threshold of dO-C2A in the development of dysphagia. In the case-control study, 34 patients were divided into two groups, as per the threshold of dO-C2A identified in the simulation study. The authors found in the simulation study that a dO-C2A of -5° delineated the threshold between normal swallowing and dysphagia. In the case-control study, that multivariate analysis showed that dO-C2A was the only variable that significantly correlated with the difference in the nasopharyngeal airway. The prevalence of dysphagia after OCF in patients with dO-C2A<-5° was as high as 66.7% (6/9) and there was no patient suffering from dysphagia in patients with dO-C2A≥-5°. The authors concluded that dO-C2A of -5° could be the angle that determines the threshold between dysphagia and normal swallowing.

Contributed by Dr. Kanwaljeet Garg

Pomeraniec IJ, et al. Early versus late gamma knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: A multicenter matched-cohort study. J Neurosurg 2018;129:648-57.

Gamma knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas (NFPM). However, there is no consensus as to whether GKRS should be used early after surgery, or it should be withheld until there is a radiological tumor progression. This study was a multicenter retrospective review of patients with NFPM who underwent trans-sphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions. The patients were matched by the characteristics of the adenoma as well its radiosurgical parameters, and stratified based on the time interval between last surgical resection and the commencement of GK radiosurgery. After the matching, 222 patients were grouped based on early (n = 111) or late (n = 111) GKRS administration following transsphenoidal surgery. The authors found that there was a greater risk of tumor progression after GKRS (P = 0.013) and the presence of residual tumor (P = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. The difference in the occurrence of post-GKRS endocrinopathy was not significant in the two groups. Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after their original presentation (P = 0.32). The authors concluded that early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late or salvage radiosurgery.

Contributed by Dr. Kanwaljeet Garg and Dr. Anant Mehrotra

Armangue T, et al. Spanish Herpes Simplex Encephalitis Study Group. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: A prospective observational study and retrospective analysis. Lancet Neurol 2018;17:760-72.

This important clinical study involved multiple centers from Spain. It described the frequency and other clinical predictors of autoimmune encephalitis after herpes simplex encephalitis. The authors completed the study in two cohorts. The cohort A had 19 participating centers, which followed their patients until one year. The cohort B patients were studied retrospectively after the development of autoimmune encephalitis. The number of patients recruited in cohort A was 54 and the number studied in cohort B was 51. During the follow up period, 27% of the patients developed autoimmune encephalitis and 100% had neuronal antibodies. The study also showed that patients aged less than four years were more likely to develop autoimmune encephalitis earlier after an episode of herpes encephalitis. The prognosis was also not good in young children. This study has significant implications for the monitoring of neuronal antibodies and administering early treatment to the patients following an episode of autoimmune encephalitis.

Contributed by Dr. Ravi Yadav

Neumann WJ, et al. Functional segregation of basal ganglia pathways in Parkinson's disease. Brain 2018;141:2655-69.

This study, done by Neumann and colleagues, studied 20 patients of Parkinson's disease who had undergone subthalamic (STN) deep brain stimulation (DBS), and 20 controls. By using clinical, behavioural and fiber tracking mathematical models, this study showed that the lack of cognitive adaptation is probably due to the variation of the hyper-direct pathway but the kinematics rely more on the suppression of the indirect pathway actions. The findings show that the hyperdirect and indirect pathways converging on the subthalamic nucleus work differently in performing the cognition and the movement task. The results of this study would help to refine further the stimulation techniques, based on the knowledge of basal ganglia circuits, to reduce the side effects of DBS.

Contributed by Dr. Ravi Yadav and Dr. Kuntal K. Das

Samaha H, et al. A homing system targets therapeutic T cells to brain cancer. Nature 2018. doi: 10.1038/s41586-018-0499-y.

The T cell immunotherapy of brain tumors has been a challenge as the T cells were unable to access the tumor and hence could not act upon it. Samaha and colleagues, in this paper, describe the experimental techniques that make the brain tumor cells accessible to T cells and immunotherapy. They explain that in comparison to the inflammatory brain diseases like multiple sclerosis where intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) are upregulated, the brain cancer cells tend to upregulate activated leukocyte cell adhesion molecule (ALCAM). The authors re-engineered ALCAM based natural ligand cluster of differentiation (CD) 6 so that the T cells could get a special route for homing (the ALCAM restricted homing system). This route is capable of capturing the circulating T cells. The above system has been shown to work strongly after an intravenous injection of T cells, thus showing that the authors have developed a new molecule that could target the delivery of T cells to brain cancers.

Contributed by Dr. Ravi Yadav

Fox RJ, et al. NN102/SPRINT-MS trial investigators. Phase 2 trial of ibudilast in progressive multiple sclerosis. N Engl J Med 2018;379:846-55.

There are not many options for treating patients with primary progressive multiple sclerosis (PPMS) at present. This study performed by Fox and colleagues tested the molecule, ibudilast, which inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and has an immunomodulatory role in PPMS. This was a phase 2 randomized trial of ibudilast versus a placebo in patients with primary or secondary progressive multiple sclerosis, lasting for 96 weeks. The primary endpoint was the rate of brain atrophy. At the end of the study period, it was found that the study drug was able to slow down the brain atrophy significantly as compared to the placebo. This was estimated to be 2.5ml of brain tissue. Thus, based on the results of this phase 2 study, the drug ibudilast could be a promising option in patients with PPMS.

Contributed by Dr. Ravi Yadav and Dr. Sahil Mehta

Bassez G, et al. Improved mobility with metformin in patients with myotonic dystrophy type 1: A randomized controlled trial. Brain 2018. doi: 10.1093/brain/awy231.

Bassez and colleagues tested metformin, the commonly used drug used in type II diabetes mellitus, for improvement in various parameters of muscle functions in patients with myotonic dystrophy type I (DM1). The basis of this study was multifactorial and included several molecular mechanisms like ribose nucleic acid (RNA) splicing, autophagia, insulin sensitivity or glycogen synthesis. Metformin also has a very good safety profile, and there are no therapeutic options in DM1. The authors recruited 40 adult patients of DM1 from the neuromuscular center of Henri Mondor Hospital and started them on escalating doses of metformin versus a placebo three times a day to a dose of 3gm/day over a period of 1 month. At the end of 1 year, 23 of 40 patients completed the study. The difference in the two groups was statistically significant with improved mobility and the total muscle power also being improved. The results of this study are encouraging and warrant a re-evaluation of these findings in a multicentric phase III trial.

Contributed by Dr. Ravi Yadav

Seshagiri DV, et al. Optokinetic nystagmus in SCA patients: A bedside test for oculomotor dysfunction grading. Neurology 2018. doi: 10.1212/WNL.6250.

This interesting paper highlights the importance of optokinetic nystagmus (OKN) testing at bedside by the use of OKN drum in patients with autosomal dominant spinocerebellar ataxia (SCA) type 1, 2 and 3. This study recruited 73 genetically confirmed patients of SCA followed by assessment of the disease severity using the International Co-Operative Ataxia Rating Scale (ICARS). Vertical OKN was impaired in 100% of the patients and completely absent in 86% patients with SCA1, 96% with SCA2, and 80% with SCA3. This study showed that a higher motor disability in SCA directly correlated with the severity of OKN dysfunction and not the ICARS oculomotor sub-score. This study proved that the assessment of OKN saccades was a better and a more sensitive bedside clinical test to measure the oculomotor dysfunction in neurodegenerative ataxias. This test holds promise to monitor the progression in other neurodegenerative conditions as well.

Contributed by Dr. Ravi Yadav

Dawkins RL, et al. Thoracolumbar injury classification and severity score in children: A validity study. Neurosurg 2018 doi https://doi.org/10.1093/neuros/nyy408.

The authors reviewed the medical records of pediatric patients with acute, traumatic thoracolumbar fractures at two Level 1 trauma centers. The Thoracolumbar Injury Classification and Severity (TLICS) score was calculated for each patient using computed tomography and magnetic resonance images, along with the neurological examination recorded in the patient's medical record. TLICS scores were compared with the type of treatment received. Receiver operating characteristic (ROC) curve analysis was employed to quantify the validity of the TLICS scoring system. TLICS calculations were completed for 165 patients. The mean TLICS score was 2.9 (standard deviation ± 2.7). Surgery was the treatment of choice in 23% of the patients. There was a statistically significant agreement between the TLICS suggested treatment and the actual treatment received (P < 0.001). The ROC curve calculated using multivariate logistic regression analysis of the TLICS system's parameters as a tool for predicting treatment, demonstrated an excellent discriminative ability, with an area under the ROC curve of 0.96, which was also statistically significant (P < 0.001). The authors concluded that the TLICS system demonstrates a good validity for selecting the appropriate thoracolumbar fracture treatment in pediatric patients.

Contributed by Dr. Anant Mehrotra

Nagahama Y, et al. Dual antiplatelet therapy in aneurysmal subarachnoid hemorrhage: Association with reduced risk of clinical vasospasm and delayed cerebral ischemia. J Neurosurg 2018;129:702-10.

The authors analysed patients treated for aneurysmal subarachnoid haemorrhage (aSAH). The patients were divided into 2 groups: Patients who underwent stent-assisted coiling or placement of flow diverters requiring dual anti-platelet therapy [DAPT] (the DAPT group); and, patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and delayed cerebral ischemia (DCI), and of hemorrhagic complications were compared between the 2 groups, utilizing univariate and multivariate logistic regression. Of the 312 aSAH patients considered for this study, 161 met the criteria for inclusion and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risks of clinical vasospasm (odds ratio [OR] 0.244, confidence interval [CI] 95% 0.097–0.615, P = 0.003) and DCI (OR 0.056, CI 95% 0.01–0.318, P = 0.001) were significantly lower in patients receiving DAPT. The rates of hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both the groups (4% vs 2%, P = 0.9). The authors concluded that the use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH, without an increased risk of hemorrhagic complications.

Contributed by Dr. Anant Mehrotra

Horton M, et al. Randomized controlled trials in adult traumatic brain injury: A systematic review on the use and reporting of clinical outcome assessments. J Neurotrauma 2018. doi: 10.1089/neu. 2018.5648.

An improvement in the study design has been viewed as a top priority for the randomized controlled trials in general and traumatic brain injury (TBI) in particular. In this regard, the use of outcome measures is receiving increasing attention. This review aimed to examine the pattern of clinical outcome assessments (COAs) used and reported in randomized control trials (RCTs) in adult patients with TBI. Systematic literature searches were conducted to identify the medium-to-large (n ≥ 100) acute and post-acute TBI trials published since 2000. Items from the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement and CONSORT patient-reported outcomes (PROs) extension were used to evaluate the reporting quality of COAs. Glasgow Outcome Scale/Extended (GOS/GOSE) data were extracted using a customized checklist. After examining a total of 126 separate COAs in 58 studies, the authors detected a heterogeneity in the use of TBI outcomes which severely limited the possible comparisons and meta-analyses of the findings of the RCT. The GOS/GOSE was included in 39 studies, but implemented in a variety of ways, rendering their comparison almost impossible. The other notable findings were a tendency to use multi-dimensional outcomes in rehabilitation settings and a paucity of the PROs, especially in acute study settings. To make the matters more difficult, the quality of reporting was variable, and key information concerning COAs was often omitted. The authors ended up recommending the following points for the future researchers: (a) To use the common data elements (CDEs) recommendations for TBI outcomes; and, (b) to follow CONSORT guidelines while publishing RCTs.

Contributed by Dr. Kuntal K. Das

Reijmer YD, et al. Microstructural white matter abnormalities and cognitive impairment after aneurysmal subarachnoid hemorrhage. Stroke 2018;49:2040-5.

It is not unusual to find cognitive impairment in patients surviving acute aneurysmal subarachnoid hemorrhage (aSAH). The same may occur despite the absence of post ictal infarction or hydrocephalus. With the hypothesis of potential white matter microstructural changes underpinning the cognitive impairments, the authors took two groups of patients for examination, aSAH group (n = 49) and unruptured intracranial aneurysm group (n = 22) and performed a high-resolution diffusion tensor imaging sequence using a 3 Tesla MRA. Patients with aSAH were again scanned after 2 weeks and 6 months of ictus. Cognition was evaluated 3 months after ictus. The patients with aSAH had higher white matter mean diffusivity (MD) 2 weeks after the ictus than patients with an unruptured intracranial aneurysm (P ≤ 0.01), reflecting an abnormal microstructure. After 6 months, the MD had returned to the level of the unruptured intracranial aneurysm group. Higher MD at 2 weeks was associated with cognitive impairment after 3 months (odds ratio per standard deviation increase in MD, 2.6; 95% confidence intervals, 1.1–6.7).

Contributed by Dr. Kuntal K. Das

Sulaiman OAR, et al. A rat study of the use of end-to-side peripheral nerve repair as a “babysitting” technique to reduce the deleterious effect of chronic denervation. J Neurosurg 2018. doi: 10.3171/2018.3.JNS172357.

In this interesting study on rats, the authors evaluated a temporary end-to-side neurorrhaphy to “babysit” (protect) the denervated distal nerve stump at the time of nerve repair and reduce the deleterious effect of chronic denervation on nerve regeneration. The very premise on which they carried out the work was that the lack of timely ingress of regenerating neurons into the nerve distal to the injury leads to non-utilization of the regeneration promoting milieu created by Schwann cells and leads to eventual irreversible changes in the muscle end plate. They used one of the hindlimbs of Sprague-Dawley rats where the common peroneal (CP) nerve was transected at the first stage and the distal end was either tied to a muscle to prevent regeneration or inserted through a perineurial window into the intact tibial (TIB) nerve, i.e., by performing a CP-TIB end-to-side neurorrhaphy. Using the retrograde dye counting technique, they demonstrated a mean of 231 ± 83 regenerating neurons across this anastomosis after 3 months in the latter group. In the second experiment, the intact TIB nerve was transected and cross-sutured to a 3-month chronically denervated distal CP nerve stump that had either been “protected” by ingrown TIB nerves after a CP-TIB neurorrhaphy or remained chronically denervated. They found a much higher number of regenerating axons and heavier tibialis anterior muscle in the protected group that substantiated their hypothesis. Such an end-to-side neurorrhaphy may be invaluable as a means of preventing the atrophy of distal nerve stumps and target organs after chronic denervation and may have a future in nerve repair.

Contributed by Dr. Kuntal K. Das

Fyllingen EH, et al. Does risk of brain cancer increase with intracranial volume? A population-based case-control study. Neuro Oncol 2018 doi: 10.1093/neuonc/noy043.

This investigation was an attempt to see if the variation in intracranial volume, as a surrogate marker of number of stem cells and the brain size, may be linked to risk of development of a high-grade glioma. The authors calculated the intracranial volume from the pretreatment three-dimensional (3D) T1-weighted magnetic resonance imaging brain scans from 124 patients with a high-grade glioma and 995 general population–based controls. To ascertain the effect of intracranial volume and gender on the likelihood of the participants to have high-grade glioma, a binary logistic regression analysis was performed. An intracranial volume of more than 100 ml had 1.7 times chances of having a high grade glioma (95% confidence interval (CI): 1.44–1.98; P < 0.001). Once the intracranial volume was adjusted, the presence of a female subject emerged as a risk factor for the development of a high-grade glioma (odds ratio for male subject = 0.56, 95% CI: 0.33–0.93; P = 0.026).

Contributed by Dr. Kuntal K. Das






 

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