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   Thomé C,
   Chen Z, et al...
   Abdu WA, et a...
   Burkhardt BW,
   Wittig JH Jr,
   Marques T, et...
   Griveau A, et...
   Happold C, et...
   Puchalski RB,
   Long GV, et a...
   Alattar AA, e...
   Chen CJ, et a...
   Elsawaf A, et...
   Johnston SC, ...
   Sprigg N, et ...
   Ghalaenovi H,
   Malcolm JG, e...
   Thevathasan W, <...
   Christison K,
   Haas- Kogan D, <...
   Gorton HC, et...
   Ioannidis JPA. t...
   Hacohen Y, et...
   Malmqvist L, ...
   Zimmermann HG, <...
   Kaufman AR, e...
   Pakdel F, et ...
   Mensing LA, e...
   Can a, et al....
   Acerbi F, et ...
   Van Lieshout JH,...
   Misawa S, et ...
   Carabenciov ID, ...
   Egan MF, et a...
   Kunutsor SK, ...
   Amarenco P, e...
   Tomson T, et ...
   Cagnazzo F, e...
   Meijerman A, ...
   Bruce CV, et ...
   Al-Ajlan FS, ...
   O'connor EE,...
   Jaja BNR, et ...
   Wilson MP, et...
   Kuo CH, et al...
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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 4  |  Page : 1141-1153

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

1 Department of Neurosurgery, Wockhardt Hospital, Mumbai, Maharashtra, India
2 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
4 Department of Radiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
5 Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication18-Jul-2018

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

DOI: 10.4103/0028-3886.237001

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How to cite this article:
Turel MK, Tripathi M, Aggarwal A, Singla N, Takkar A, Mehta S, Ahuja CK, Mehrotra A, Das KK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India 2018;66:1141-53

How to cite this URL:
Turel MK, Tripathi M, Aggarwal A, Singla N, Takkar A, Mehta S, Ahuja CK, Mehrotra A, Das KK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India [serial online] 2018 [cited 2018 Aug 17];66:1141-53. Available from:

Thomé C, et al. Annular Closure in Lumbar Microdiskectomy for Prevention of Reherniation: a Randomized Clinical Trial. Spine J 2018 Doi: 10.1016/j.spinee. 2018.05.003.

The authors conducted a multicenter, randomized superiority study to determine whether a bone-anchored annular closure device (ACD) in addition to lumbar microdiskectomy resulted in lower re-herniation and reoperation rates along with increased overall success compared to lumbar microdiskectomy alone. 550 patients (ACD: n = 267; control: n = 283) were included for this purpose. Both co-primary endpoints of the study were met, with recurrent herniation and composite endpoint success favouring ACD. The frequency of symptomatic reherniation was lower with ACD (12% vs. 25%). There were 29 reoperations in 24 patients in the ACD group and 61 reoperations in 45 control patients. The frequency of reoperations to address recurrent herniation was 5% with ACD and 13% in controls. End plate changes were more prevalent in the annular closure device group (84% vs 30%). Scores for back pain, leg pain, Oswestry Disability Index, and health-related quality of life at regular visits were comparable between the groups over a 2-year follow-up.

Contributed by Dr. Mazda K Turel

Chen Z, et al. Percutaneous Transforaminal Endoscopic Discectomy Compared With Microendoscopic Discectomy for Lumbar Disc Herniation: 1-Year Results of an Ongoing Randomized Controlled Trial. J Neurosurg Spine 2018;28:300-10.

A prospective randomized controlled study was conducted in 153 patients to clarify whether percutaneous transforaminal endoscopic discectomy (PTED) resulted in better clinical outcomes and less surgical trauma than microendoscopic discectomy (MED). The primary outcome was the Oswestry Disability Index (ODI) score 1 year after surgery. Primary and secondary outcomes did not differ significantly between the treatment groups at each prespecified follow-up point. For PTED, there was a lesser postoperative improvement in the ODI score in the median herniation subgroup compared with the paramedian subgroup; whereas for MED, there was a significantly lesser improvement in the ODI score in the far- lateral herniation subgroup compared with the paramedian subgroup at one year. The total complication rate over the course of 1 year was 14% in the PTED group and 16% in the MED group. Five patients (6.25%) in the PTED group and 3 patients (4.11%) in the MED group suffered from residual herniation/recurrence of herniation, for which reoperation was required. Over the 1-year follow-up period, PTED did not show superior clinical outcomes and did not seem to be a safer procedure for patients with lumbar disc herniation compared with MED. As one would expect, PTED had inferior results for median disc herniation, whereas MED did not seem to be the best treatment option for far-lateral disc herniation.

Contributed by Dr. Mazda K Turel

Abdu WA, et al. Long-Term Results of Surgery Compared With Non-Operative Treatment for Lumbar Degenerative Spondylolisthesis in the Spine Patient Outcomes Research Trial (SPORT). Spine (Phila Pa 1976). 2018 Doi: 10.1097/brs.0000000000002682.

The authors compared eight-year outcomes between surgery and non-operative care for symptomatic lumbar degenerative spondylolisthesis (DS). The treatment consisted of standard decompressive laminectomy (with or without fusion) versus the standard non-operative care. Primary outcome measures were the Short Form-36 (SF-36) scores and the modified Oswestry Disability Index at six weeks, three months, six months and yearly up to eight years. Data were obtained for 69% of the randomized cohort and 57% of the observational cohort at the eight-year follow up. As-treated analyses in the randomized and observational groups showed significantly greater improvement in the surgery group on all primary outcome measures at all time points through eight years. Outcomes were similar among patients treated with an un-instrumented posterolateral fusion, instrumented posterolateral fusion, and 360° fusion. Among patients with symptomatic DS, those patients who received surgery had a significantly greater improvement in pain and function compared to non-operative treatment through eight years of follow-up. The fusion technique did not affect outcomes.

Contributed by Dr. Mazda K Turel

Burkhardt BW, et al. Clinical Outcome Following Anterior Cervical Discectomy and Fusion With and Without Anterior Cervical Plating for the Treatment of Cervical Disc Herniation - a 25-Year Follow-Up Study. Neurosurg Rev 2018;41:473-82.

Extremely long-term clinical outcomes following anterior cervical discectomy and fusion (ACDF) with an autologous iliac crest graft with and without Caspar plating (ACDF + CP) for the treatment of radiculopathy caused by cervical disc herniation (CDH) are very rarely reported. Hospital records of patients who underwent ACDF or ACDF + CP for the treatment of CDH at least 17 years ago were reviewed. At final follow-up, patients were reviewed with Neck Disability Index (NDI), Odom's criteria, a modified EuroQol (EQ)-5D questionnaire, and limitations in quality of life. 122 patients with a mean follow-up of 25 years were evaluated. ACDF was performed in 80 and ACDF + CP in 42 patients, respectively. At the final follow-up, 81% of patients were free of radicular pain and had no repeated procedures. According to the Odom's criteria, 86% of good-to-excellent functional recovery was noted. The mean NDI and EQ-5D were 14% and 5 points, respectively. There was no significant difference in the assessed clinical outcome parameters between patients treated with ACDF and ACDF + CP. The rate for a repeated procedure due to the presence of a degenerative cervical disorder was 11%, out of which 7% were due to the symptomatic adjacent segment disease. ACDF and ACDF + CP achieved a high rate of radicular pain relief (89%) and clinical success (86%) for the treatment of CDH within a 25-years follow-up. No statistical difference concerning the clinical outcome and the rate of repeated procedure was detected.

Contributed by Dr. Mazda K Turel

Wittig JH Jr, et al. Attention Improves Memory by Suppressing Spiking-Neuron Activity in the Human Anterior Temporal Lobe. Nat Neurosci 2018 Doi: 10.1038/s41593-018-0148-7.

The authors identify a memory-specific attention mechanism in the human anterior temporal lobe, an area implicated in semantic processing and episodic memory formation. To identify attention mechanisms that enhance memory, they recorded intracranial electroencephalograms in 18 epileptic neurosurgery patients as they memorized words that were cued by a row of asterisks. Spiking neuronal activity is suppressed and becomes more reliable in preparation for verbal memory formation. Intracranial electroencephalography signals implicate this region as a source of executive control for attentional selection. Consistent with this interpretation, its surgical removal causes significant memory impairment for attended words relative to unattended words. These results implicate a critical role for the preparatory suppression effects of an anterior temporal lobectomy, making the semantic concepts and meanings of our experiences more salient for improved memory formation.

Contributed by Dr. Mazda K Turel

Marques T, et al. The Functional Organization of Cortical Feedback Inputs to Primary Visual Cortex. Nat Neurosci 2018;21:757-64.

Cortical feedback is thought to mediate cognitive processes like attention, prediction, and awareness. Understanding its function requires identifying the organizational logic of feedback axons relaying different signals. The authors measured retinotopic specificity in inputs from the lateromedial visual area in mouse primary visual cortex (V1) by mapping receptive fields in feedback boutons and relating them to those of neurons in their vicinity. Lateromedial visual area inputs in layer 1 targeted, on an average, retinotopically matched locations in V1, but many of them relayed distal visual information. Orientation-selective axons overspread around the retinotopically matched location perpendicularly to their preferred orientation. Direction-selective axons that were biased to visual areas shifted from the retinotopically matched position along the angle of their anti-preferred direction. Their results show that feedback inputs show tuning-dependent retinotopic specificity. By targeting locations that would be activated by stimuli orthogonal to or opposite to a cell's own tuning, feedback could potentially enhance visual representations in time and space.

Contributed by Dr. Mazda K Turel

Griveau A, et al. A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment. Cancer Cell 2018;33:874-89.

Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. The authors show that Olig2+ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to an innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2+ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-vascular endothelial growth factor (VEGF) treatment in preclinical models and patients. Thus, glial-encoded pathways regulate distinct glioma vascular microenvironmental interactions.

Contributed by Dr. Mazda K Turel

Happold C, et al. Do Statins, ACE Inhibitors or Sartans Improve Outcome in Primary Glioblastoma? J Neurooncol 2018;138:163-71.

Recently, data from clinical studies assessing the role of co-medications in different cancer types suggested reduced mortality and potential anti-tumor activity for statins, angiotensin-I converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (sartans). Here, the authors analysed the association of co-treatment with statins, ACEI or sartans with outcomes in a cohort of 810 patients. Progression-free survival (PFS) and overall survival (OS) were analysed for each medication in the pooled patient group. No association was found for co-medication with either drug for progression free survival (PFS) or overall survival (OS). The median OS was 22.1 (statins) versus 22.2 (control) months, 20.4 (ACEI) versus 22.6 (control) months, and 21.7 (sartans) versus 22.3 (control) months. This secondary analysis of two large glioblastoma trials thus was unable to detect any benefit with the use of statins, ACEI or sartans on the outcomes in patients with newly diagnosed glioblastoma. These data challenge the rationale for prospective studies on the possible role of these non-tumor-specific drugs within the concept of drug repurposing.

Contributed by Dr. Mazda K Turel

Puchalski RB, et al. An Anatomic Transcriptional  Atlas More Details of Human Glioblastoma. Science 2018;360:660-3.

Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. The authors present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning the molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment.

Contributed by Dr. Mazda K Turel

Long GV, et al. Combination Nivolumab and Ipilimumab or Nivolumab Alone in Melanoma Brain Metastases: a Multicentre Randomised Phase 2 Study. Lancet Oncol 2018;19:672-81.

The authors aimed to establish the efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with active melanoma brain metastases. This multicentre open-label randomised phase 2 trial was conducted at four sites in Australia, in three cohorts of immunotherapy-naive patients aged 18 years or older, in 79 patients with melanoma brain metastases. The authors concluded that nivolumab combined with ipilimumab and nivolumab monotherapy are active in melanoma brain metastases. A high proportion of patients achieved an intracranial response with the combination. No treatment-related deaths occurred. Thus, the authors concluded that nivolumab combined with ipilimumab should be considered as a first-line therapy for patients with asymptomatic untreated brain metastases.

Contributed by Dr. Mazda K Turel

Alattar AA, et al. Risk Factors of Readmission With Cerebrospinal Fluid Leakage Within 30 Days of Vestibular Schwannoma Surgery. Neurosurgery 2018;82:630-7.

Cerebrospinal fluid (CSF) leak is a well-recognized complication after vestibular schwannoma (VS) surgery and is associated with a number of secondary complications, including readmission and meningitis. The authors aimed to identify the risk factors for and the timing of 30-day readmission with CSF leak after surgical resection of VS. A total of 6820 patients were identified. CSF leak, though a relatively uncommon cause of admission after discharge (3.5% of all patients), was implicated in nearly half of 490 re-admissions. Significant independent predictors of re-admission with CSF leak were male sex, first admission at a teaching hospital, CSF leak during the first admission, obesity during the first admission and case volume of the first admission hospital. The median time to readmission was 6 days from the time of hospital discharge. The authors propose that surgeons should focus on technical factors that may reduce CSF leakage and take advantage of the potential screening strategies for the detection of CSF leakage prior to the first post-admission discharge.

Contributed by Dr. Mazda K Turel

Chen CJ, et al. Microsurgery Versus Stereotactic Radiosurgery for Brain Arteriovenous Malformations: a Matched Cohort Study. Neurosurgery 2018 Doi: 10.1093/neuros/nyy174.

The authors conducted this study to compare the outcomes of microsurgery (MS) and stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVM), through a retrospective, matched cohort study in 59 patients. The primary outcome was defined as AVM obliteration without the appearance of a new permanent neurological deficit. Both radiological (85 vs 11 months) and clinical (92 vs 12 months) follow-ups were significantly longer for the SRS cohort. The primary outcome was achieved in 69% of each cohort. The MS cohort had a significantly higher obliteration rate (98% vs 72%), but also had a significantly higher rate of new permanent deficit (31% vs 10%). The posttreatment hemorrhage rate was significantly higher for the SRS cohort (10% for SRS vs 0% for MS). In subgroup analyses of ruptured and unruptured AVMs, no significant differences between the primary outcomes were observed. The authors concluded that for patients with comparable AVMs, MS and SRS afford similar rates of deficit-free obliteration. Nidal obliteration is more frequently achieved with MS, but this intervention also incurs a greater risk of new permanent neurological deficit.

Contributed by Dr. Mazda K Turel

Elsawaf A, et al. Decompressive Craniotomy for Malignant Middle Cerebral Artery Infarction: Optimal Timing and Literature Review. World Neurosurg 2018 Doi: 10.1016/j.wneu.2018.04.005.

A prospective randomised study was done to compare the results of early or delayed decompressive craniotomy (DC) for cases of malignant middle cerebral artery (MCA) infarction on a consecutive series of 46 patients. Patients were divided randomly into two groups: Group I consisted of 27 patients who were followed till obvious deterioration of conscious level occurred; and, Group II consisted of 19 patients who were operated prophylactically within 6 hours of their presentation even with no clear deterioration of their consciousness level or of radiology findings. At the final follow-up, both groups showed a good improvement in the consciousness level, motor power, and functional outcome; however, statistically significant neurological improvement was demonstrated in group II. Functional outcome also showed statistically significant improvement in this ultra-early decompression group (group II). There was a significant difference in mortality in both the groups as more than half (52%) of group I patients died due to the delay in surgery or its other consequences. Another significant difference was in the progression of infarction volume, which was observed in group I more frequently. The authors concluded that an early DC, within 6 hours of the ictus, without waiting for neurological deterioration has a significant impact on prognosis, despite its possible complications. Avoiding a delay in transferring the case, in diagnosing the condition or in taking the decision of surgery, will significantly affect the mortality and overall outcome.

Contributed by Dr. Mazda K Turel

Johnston SC, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med 2018 Doi: 10.1056/NEJMoa1800410.

In a randomized trial, the authors assigned patients with minor ischemic stroke or high-risk transient ischemic attack (TIA) to receive either clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day), or the same range of doses of aspirin plus a placebo. A total of 4881 patients were enrolled at 269 international sites. Major ischemic events occurred in 5% of patients receiving clopidogrel plus aspirin and in 6.5% patients receiving aspirin plus a placebo (P = 0.02), with most events occurring during the first week after the initial event. Major hemorrhage occurred in 23 patients (0.9%) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus a placebo (P = 0.02). The authors concluded that in patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone.

Contributed by Dr. Mazda K Turel

Sprigg N, et al. Tranexamic Acid for Hyperacute Primary Intra Cerebral Hemorrhage (TICH-2): an International Randomised, Placebo-Controlled, Phase 3 Superiority Trial. Lancet 2018 Doi: 10.1016/s0140-6736(18)31033-X.

In this international, randomised, placebo-controlled trial of adults with intracerebral haemorrhage, 2325 participants with a mean age of 69 years received 1 g intravenous tranexamic acid bolus followed by an infusion of another 1 g intravenous tranexamic acid over 8 h, or a matching placebo, within 8 h of symptom onset. The primary outcome was functional status at day 90, measured by a shift in the modified Rankin Scale (mRS). Unfortunately, TICH-2 found no significant difference in the functional status 90 days after the occurrence of intracerebral haemorrhage with tranexamic acid. Additionally, there was no difference between the tranexamic acid and placebo groups in the proportion of participants who were dead or dependent at day 90 despite a reduction in the early deaths and serious adverse events. Thus, TICH-2 showed the safety of tranexamic acid but not an improvement in the functional status at 90 days.

Contributed by Dr. Mazda K Turel

Ghalaenovi H, et al. The Effects of Amantadine on Traumatic Brain Injury Outcome: a Double-Blind, Randomized, Controlled, Clinical Trial. Brain Inj 2018 Doi: 10.1080/02699052.2018.1476733.

Amantadine, as a dopamine receptor agonist, may stimulate and help in the recovery of the nervous system after traumatic brain injury (TBI). The authors performed this study as a double-blind, randomized, controlled clinical trial including 40 patients with TBI who scored nine or lower on the Glasgow Coma Scale (GCS), admitted to the hospital. The protocol included administration of the drug (placebo or amantadine) for 6 weeks and patient evaluation using the GCS and FOUR score on the first, third and seventh days after the drug was started. After 6 months from starting the study drug, the patients were evaluated on the Mini-Mental State Examination, Glasgow Outcome Study, Disability Rating Scale and Karnofsky Performance Scale. The mean age of the patients was 37 years. As an only important finding, the amantadine group registered an important rise between the first and the seventh day of the study drug. Based on their findings during the first week and the 6-month (since starting drug) follow-up, prescribing amantadine did not lead to reportable effects on the patients' level of consciousness, memory, disability, cognition, mortality and performance.

Contributed by Dr. Mazda K Turel

Malcolm JG, et al. Autologous Cranioplasty Is Associated With Increased Re- Operation Rate: a Systematic Review and Meta-Analysis. World Neurosurg 2018 Doi: 10.1016/j.wneu.2018.05.009.

Consensus regarding selection of a synthetic versus an autologous flap re-implantation for cranioplasty after a decompressive craniectomy has not been reached and the multiple factors considered for each patient make the comparative analysis challenging. This study examined the association between the choice of material and the related complications.

A systematic literature review and meta-analysis was performed using PubMed for articles reporting the results of a delayed cranioplasty after decompressive craniectomy using a cohort design comparing autologous bone and synthetic implants. One randomized controlled trial and eleven cohort studies were included for a total of 1586 implants (950 bone, 636 synthetic). Autologous implants had significantly more reoperation rates than synthetic implants. Reoperations were most often due to resorption (54%) followed by infection (41%). The pooled incidence of resorption in autologous implants was 20%. Among the other outcomes, there was no significant difference in the occurrence of infections or wound related complications.

Contributed by Dr. Mazda K Turel

Thevathasan W, et al. Pedunculopontine Nucleus Deep Brain Stimulation in Parkinson's Disease: a Clinical Review. Mov Disord 2018;33:10-20.

Among all the indications for deep brain stimulation surgery, idiopathic  Parkinsonism More Details is the most common one. Globus pallidus interna (GPi) and subthalamic nucleus (STN) are the two most common and popular targets. Both of these targets are effective in alleviating symptoms of rigidity, tremor and bradykinesia but provide poor results in controlling axial symptomatology of gate freezing and postural instability. Animal studies have earlier shown occasional good outcomes with targeting of the pedunculopontine nucleus (PPN) in controlling this symptomatology. This target and its role in controlling the gait related symptomatology had been discovered nearly a decade ago, yet there is no conclusive evidence in its support as the cohort of implanted patients worldwide remains quite limited. The authors have meticulously summarized the literature related to the clinical application of PPN DBS employed to date. However, some conclusions can still be drawn: A. PPN DBS has the potential to improve gait freezing in both off and on medication states and can reduce falls in some patients. B. Literature is not sure about the impact of the procedure on postural instability. C. PPN DBS does not improve other aspects of the gait such as gait akinesia. D. There is no substantial change in the dosage of dopaminergic medication requirements. E. There is no substantial change in the cognitive outcome of the patient. These modest results demand further well-designed randomized controlled trials to assess the impact of PPN DBS in various spheres of the disease.

Contributed by Dr. Manjul Tripathi

Christison K, et al. Intermittent Catheterization: the Devil in the Details. J Neurotrauma 2018;35:985-9.

Management of a neurogenic lower urinary tract dysfunction (NLUTD) is a non-standardized territory of management amongst neurosurgical patients suffering from various spinal cord ailments such as spinal cord trauma and spinal dysraphism. In 2014, a Cochrane review by Prieto et al., “Intermittent catheterisation for long term bladder management” became a leading document that changed many prevailing practices. This document concluded that there is still no convincing evidence that the incidence of urinary tract infections (UTI) is affected by the use of aseptic or clean technique, coated or uncoated catheters, single (sterile) or multiple-use (clean) catheters, self or assisted catheterisation or by any other strategy. Such conclusions made a significant impact on the prevailing practices. Christison et al., have reanalyzed the same data in the wake of updated definition of catheter associated UTI with identification of the faults in the study design and derived new conclusions. Though there was no difference found between single versus multiple use of catheters, the use of hydrophilic versus other catheters demonstrated a significantly lower incidence of UTI with hydrophilic catheters. Till the availability of next level of evidence, the single use of catheters should be encouraged as catheter cleaning is a major issue and there is no universally accepted cleaning method. I personally believe that an optimal bowel and bladder control in patients of NLUTD is the major responsibility of health care providers which significantly affects the quality of life, health care expenditure, and disability adjusted life years (DALYs) of any individual.

Contributed by Dr. Manjul Tripathi

Haas- Kogan D, et al . National Cancer Institute Workshop on Proton Therapy for Children: Considerations Regarding Brainstem Injury. Int J Radiation Once Biol Phys 2018;101:152-68.

Every new treatment modality generates controversy and comparisons with the existing standards of care. The growing application of proton radiosurgery is also facing the same problems. The particle based proton radiosurgery is a four-decade old technique, which primarily could not become popular because of the high cost of treatment and its poor availability in most parts of the globe. The Bragg peak effect assured by proton beam radiosurgery offers a higher degree of safety to the adjoining brain parenchyma as well as along the tract of radiation. Apart from its uage in chordomas, proton beam radiosurgery is now routinely being utilized for paediatric posterior fossa tumors. Brainstem necrosis is a devastating though rare complication of radiation therapy. The three largest US paediatric proton therapy units have evaluated 671 patients over a decade-long experience after proton beam radiosurgery and have estimated brain stem toxicity in the range of 2.38%. Following this analysis, new guidelines for treatment planning have emerged and the current consensus regarding the brainstem constraints for proton therapy are presented in this article, which has successfully reduced the toxicity profile to 0%. The proposed radiation parameters need to be properly evaluated and adequately followed for maintaining a good safety margin while providing an optimal long-term care.

Contributed by Dr. Manjul Tripathi

Gorton HC, et al. Risk of Unnatural Mortality in People With Epilepsy. JAMA Neurol 2018. Doi: 10.1001/jamaneurol.2018.0333.

An epileptic patient is at a 2-3 times higher risk of dying prematurely. This wide population-based research has tried to identify the causes of natural and unnatural deaths among the patient population in England and Wales. This study reports that epileptic patients are at a 2-5 fold increased risk of unnatural mortality by suicides, homicides, unintentional injury or poisoning. An epileptic patient has an overall increased suicidal tendency due to easy accessibility of anti-epileptic drugs and other medications prescribed to treat co-morbidities. The drugs responsible for death are usually psychotropic drugs or opioids. Whether or not the neural pathways governing suicidality and epilepsy are also common, needs to be further evaluated. Clinicians should also explore any symptoms of mental illness in the people with epilepsy, especially the presence of any self-harming behavior, and drugs should be judiciously prescribed with proper counselling and special emphasis on simultaneously administering drugs that also address the co-morbid conditions.

Contributed by Dr. Manjul Tripathi

Ioannidis JPA. the Proposal to Lowerpvalue Thresholds To.005. JAMA 2018;319:1429-30.

There is a popular saying in the scentific literature, “There are lies, there are bad lies, and there are statistics.” This interesting article by a statistician is an attempt to prevent the widespread corruption of world literature by the publication hungry population. Determination of a P value provides a probability that the proposed hypothesis is true. This definition has multiple misinterpretations, and better looking P values do not always guarantee transparency or confidence of the data. This article suggests several solutions for strengthening the data and results. Lowering the value of P to 0.005 from 0.05 would be a rather simple temporizing measure but would be ineffective in the long term. Lowering this value will make previously established parameters from definite to suggestive recommendations. The P value thresholds should be abandoned and the exact P value should be used. This insightful view point by the author is thought provoking and should be encouraged by the publishing houses, reviewers, and researchers to maintain a high level of clinical evidence and confidence.

Contributed by Dr. Manjul Tripathi

Hacohen Y, et al. Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody–associated Disease. JAMA Neurol 2018;75:478-87.

Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently being identified in a range of demyelinating disorders in adults and children. This prospective study collected demographic, clinical, and radiologic data from 102 patients from 8 countries of the European Union Paediatric Demyelinating Disease Consortium to evaluate the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab–associated disease. Annualized relapse rates (ARRs) and Expanded Disability Status Scale (EDSS) scores before and during treatment with disease-modifying drugs were evaluated. In all, 464 demyelinating events were reported. Although commonly used to treat patients with multiple sclerosis, disease modifying agents (such as interferons or glatiramer acetate) were not associated with clinical improvement in children with MOG-Ab–associated disease, whereas azathioprine, mycophenolate mofetil, rituximab, and particularly intravenous immunoglobulins were associated with a reduction in the relapse frequency. The establishment of the correct diagnosis of relapsing MOG-Ab–associated disorders is, therefore, important to optimize immune treatment.

Contributed by Dr Aastha Takkar

Malmqvist L, et al. Optic Disc Drusen in Children: the Copenhagen Child Cohort 2000 Eye Study. J Neuroophthalmol 2018;38:140-6.

Optic disc drusen (ODD) are seen in up to 2.4% of the general population, but the etiology and pathophysiology of the condition is still unknown. The purpose of this observational, longitudinal population-based birth cohort study, with a nested case–control, that included 1,406 children, was to determine the prevalence of

ODD in a population-based child cohort and to determine if scleral canal diameter and fetal birth and pubertal parameters are associated with the presence of ODD.

Eye examinations were performed when the children were between 11 and 12 years of age. Assessment of optical coherence tomography (OCT) scans from 1,304 children with gradable enhanced depth imaging scans of the optic disc was done.

The prevalence of ODD was 1% in a large child cohort examined by OCT. ODD was found only in eyes with a narrow scleral canal, which is consistent with the hypothesis that ODD might arise as a consequence of retinal nerve fiber congestion in the scleral canal.

Contributed by Dr Aastha Takkar

Zimmermann HG, et al . Association of Retinal Ganglion Cell Layer Thickness With Future Disease Activity in Patients With Clinically Isolated Syndrome. JAMA Neurol Doi: 10.1001/jamaneurol.2018.1011.

Clinically isolated syndrome (CIS) describes a first clinical incident suggestive of multiple sclerosis (MS). Identifying patients with CIS who have a high risk of future disease activity and then establishing a subsequent diagnosis of MS has always remained a crucial part of the management of the disease. This prospective, longitudinal cohort study investigated the association of the results of retinal optical coherence tomography (OCT) with future disease activity in 179 patients with CIS at 2 German tertiary referral centers. The primary outcome was not meeting the 'no evidence of disease activity' (NEDA-3) criteria; secondary outcomes were the establishment of diagnosis of MS and the worsening of disability. A total of 97 of the 179 screened patients were enrolled in the study Of the 97 patients with CIS, 58 did not meet the NEDA-3 criteria during the follow-up period. A Kaplan-Meier analysis showed a significant probability difference in not meeting the NEDA-3 criteria by ganglion cell and inner plexiform layer thickness A follow-up diagnosis of MS was more likely in patients with a low ganglion cell layer and inner plexiform layer thickness Retinal ganglion cell and inner plexiform layer thickness might prove to be a valuable imaging marker for anticipating future disease activity and for establishing the diagnosis of MS in patients with CIS, which can potentially support patient monitoring and the initiation of disease-modifying therapy.

Contributed by Dr Aastha Takkar

Kaufman AR, et al . Herpes Zoster Optic Neuropathy. J Neuroophthalmol 2018;38:179-89.

This was an interesting retrospective chart review performed at multiple academic eye centers to characterize the clinical features, therapeutic choices, and visual outcomes in Herpes zoster optic neuropathy (HZON). All the eyes presenting with optic neuropathy within 1 month of affliction with cutaneous Herpes zoster of the ipsilateral trigeminal dermatome were included in the study. Optic neuropathy was anterior in 2 eyes and retrobulbar in 4. Other manifestations of HZON included keratoconjunctivitis and iritis. All the patients were treated with systemic antiviral therapy in addition to topical and/or systemic corticosteroids. At the last follow-up, visual acuity in 3 eyes had improved relative to the initial presentation, 2 eyes had worsened, and 1 eye remained the same. The 2 eyes that did not receive systemic corticosteroids had the best observed final visual acuity. Visual recovery after HZON is variable. While adequate information on the identification of an optimal treatment regimen for HZON could not be obtained in this study, systemic antiviral agents remained the cornerstone of treatment. The efficacy of systemic corticosteroids remains unclear.

Contributed by Dr Aastha Takkar

Pakdel F, et al. Erythropoietin in Treatment of Methanol Optic Neuropathy. J Neuroophthalmol 2018;38:167-71.

Optic neuropathy due to methanol poisoning has often being considered severe and irreversible. In this prospective, noncomparative interventional case series, the authors evaluated the potential neuroprotective effect of erythropoietin (EPO) on visual acuity (VA) in patients with methanol optic neuropathy. 16 consecutive patients (32 eyes) with methanol optic neuropathy after alcoholic beverage ingestion were included. All patients initially received systemic therapy including metabolic stabilization and detoxification with intravenous recombinant human EPO 20,000 units/day for 3 successive days. Depending on the clinical response, some patients also received a second course of EPO. VA, fundoscopy, and spectral domain optical coherence tomography were assessed during the study. The median VA in the better eye of each patient before treatment was light perception, and a significant improvement in the VA was noted at the last follow up visit after treatment with EPO. The patient's age and the time to initiate EPO treatment after methanol ingestion were not significantly related to the final VA. Intravenous EPO appeared to improve VA in patients with methanol optic neuropathy and may represent a promising treatment for this disorder. Further studies are, however, needed to substantiate this hypothesis.

Contributed by Dr Aastha Takkar

Mensing LA, et al. Perimesencephalic Hemorrhage: a Review of Epidemiology, Risk Factors, Presumed Cause, Clinical Course, and Outcome. Stroke 2018;49:1363-70.

There is a distinct subset of patients presenting with subarachnoid hemorrhage (SAH) in the perimesencephalic area who have no demonstrable aneurysms on angiography. The present study is a systematic review and meta-analysis of previous such studies. The incidence of perimesencephalic hemorrhage (PMH) was 0.5 per 100.000 person years. The mean age was 52 years with a slight male preponderance. Positive association was found with hypertension, hypercholesterolemia, hypertriglyceridemia, history of smoking and diabetes mellitus. Nearly all patients had a GCS of 15/15 at presentation. The causes of PMH included a venous source of bleeding due to a primitive pattern of venous drainage that occurred directly into the dural venous sinuses. The other causes included venous hypertension and non-aneurysmal arterial causes. Complications included hydrocephalus that occurred in 14% patients. The development of delayed cerebral ischemia (DCI) after PMH is controversial. At discharge and follow up, a large majority of the patients had a Rankin score of 0 to 2. The authors noted that these patients only required symptomatic therapy without there being any role of preventive therapy for vasospasm. Majority of them could be discharged 24 hours after the ictus.

Contributed by Dr. Ashish Aggarwal and Dr. Navneet Singla

Can a, et al. Lipid-Lowering Agents and High HDL (High-Density Lipoprotein) Are Inversely Associated With Intracranial Aneurysm Rupture. Stroke 2018;49:1148-54.

The association of various lipid fractions and lipid lowering agents with aneurysmal subarachnoid hemorrhage (SAH) has been controversial. In the present case control study, the roles of total cholesterol, HDL, LDL, and the use of lipid-lowering agents on the risk of SAH were studied in a total of 4701 patients with 6411 aneurysms, of which 1302 (27.7%) were ruptured. The authors factored in a variety of confounding factors such as gender, smoking, and alcohol intake and demonstrated no significant association between total serum cholesterol and the risk of SAH. This is in contrast to the findings of several other earlier studies. Previous authors have given different hypothesis to support their findings of the association between total serum cholesterol and the risk of SAH. In consonance with the previous studies, the present study found an inverse association between the HDL levels and SAH. Lipid-lowering agents had a significant inverse association with aneurysmal SAH. This action might be because of the ability of statins to enhance endothelial function and attenuate oxidative stress and inflammation in the vascular wall. The authors support the need for lipid lowering agents in patients with unruptured aneurysms.

Contributed by Dr. Ashish Aggarwal and Dr. Navneet Singla

Acerbi F, et al. The Role of Indocyanine Green Videoangiography With FLOW 800 Analysis for the Surgical Management of Central Nervous System Tumors: an Update. Neurosurg Focus 2018;44:e6.

Indocyanine green video angiography (ICG-VA) has been used in vascular neurosurgery for visualizing the blood flow in cerebral vasculature. The authors have proposed an extension of the technique to study the vascular pathophysiology in central nervous system (CNS) tumors using FLOW 800 software. A total of 71 CNS tumors (cerebral and spinal) were included in the study. The possible applications of the technique included a presurgical exploration of the sinus patency and the course of veins, the identification of neo-vascularization, checking the patency of vasculature after surgery, etc. Another important role was identification of posterior median sulcus for facilitating a dorsal midline myelotomy for intra-medullary tumors.

Contributed by Dr. Ashish Aggarwal and Dr. Navneet Singla

Ramchandran S, et al. The Impact of Different Intraoperative Fluid Administration Strategies on Postoperative Extubation Following Multilevel Thoracic and Lumbar Spine Surgery: a Propensity Score Matched Analysis. Neurosurgery. 2018. Doi: 10.1093/neuros/nyy226.

Spinal instrumentation surgery has shown a rapid advance in the recent years. This has been made possible by the better understanding of spinal anatomy, biophysics and the introduction of better instrumentation techniques. However, long segment spinal surgeries still have their own drawbacks in the form of excessive soft tissue dissection leading to triggering of a cascade of systemic inflammatory responses. This soft tissue trauma and inflammatory response leads to disturbance of vascular integrity and rapid shifts in the intravascular – extravascular fluid compartments. These fluid shifts can contribute to delayed extubation with its consequent drawbacks. The authors studied appropriate fluid requirements during prolonged spinal surgery and an increasing estimated blood loss in 246 patients. They found that patients who were promptly extubated had reduced crystalloid: colloid ratios and conversely, patients in the delayed extubation group (DEX) had increasing ratios of crystalloid: colloid infusion. In addition, the DEX group had increased morbidity.

Contributed by Dr. Ashish Aggarwal and Dr. Navneet Singla

Van Lieshout JH, et al. Perprocedural Aneurysm Rerupture in Relation to Timing of Endovascular Treatment and Outcome. J Neurol Neurosurg Psychiatry. 2018;31. Doi: 10.1136/jnnp-2018-318090.

The authors in this study wanted to state that emergency occlusion (within 6 hrs) of ruptured, intracranial aneurysms by endo-vascular means were associated with higher chances of per-procedural rupture, which could directly translate into added morbidity and mortality. Out of the 471 consecutive patients of aneurysmal rupture treated by coil embolization, 12 patients had a per-procedural rupture. Out of these 12 patients, 7 were treated within 6 hrs. Five of these 7 patients (71.4%) died during admission. There was no difference in the World Federation of Neurosurgical Societies (WFNS) grade within the procedural re-rupture and non-rupture groups. These results were contradictory to various earlier studies which showed better results with an early treatment. However, almost all of these previous studies took <72 hrs as the criteria of early treatment.

Contributed by Dr. Ashish Aggarwal and Dr. Navneet Singla

Misawa S, et al . Safety and Efficacy of Eculizumab in Guillain Barre Syndrome: a Multicenter, Double Blind, Randomized Phase 2 Trial. Lancet Neurol 2018;17:519-29.

Eculizumab is a humanized monoclonal antibody that binds directly to complement protein 5 and inhibits the formation of membrane attack complex. Advances in the immunopathogenesis of Guillain Barre syndrome suggests the role of activation of the complement pathway, leading initially to conduction block and finally to the axonal degeneration. Literature mentions 5% mortality and 20% residual disability after 1 year of the disease even after intravenous immunoglobulin (IVIg) administration or plasmapheresis. This multicenter randomized trial conducted across 13 hospitals in Japan studied the safety and efficacy of this new drug as an add on medication to the intravenous immunoglobulin therapy at 4 weeks. 23 patients were allocated to the eculizumab group and 11 to the placebo group. Though there was significant improvement in GBS functional grade score in the eculizumab group, it did not reach the prespecified response rate threshold of 50%. Further, three patients developed complications (anaphylaxis, intracranial hemorrhage and abscess) in the eculizumab group.

Contributed by Dr. Sahil Mehta

Carabenciov ID, et al . Safety of Lumbar Puncture Performed on Dual Antiplatelet Therapy. Mayo Clin Proc 2018;93:627-9.

Practice guidelines usually recommend delaying lumbar puncture (LP) in patients on dual antiplatelet therapy to prevent potentially serious but rare complications like the development of an epidural hematoma (2%). This retrospective study done at Mayo Clinic reviewed the records of 100 patients who underwent lumbar puncture on dual antiplatelet therapy, including their follow-up status for the first 3 months. The authors found no serious complications such as epidural hematoma in their case series. Traumatic LP, defined as 100 red blood cells (RBCs) per microliter, occurred in 8% cases and a bloody LP, defined as 1000 RBC's per microliter occurred in 4% cases. Although it is a small and a retrospective study, it suggests that one can go for an urgent LP even in patients on dual antiplatelet therapy thus avoiding diagnostic delays.

Contributed by Dr. Sahil Mehta

Egan MF, et al . Randomized Trial of Verubecestat for Mild-To- Moderate Alzheimer's Disease. N Engl J Med 2018;378:1691-1703.

Alzheimer's disease is characterized by the deposition of Aβ amyloid and neurofibrillary tangles. Cleavage of amyloid precursor protein by β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE) and δ secretase leads to production of amyloid beta. Verubecestat is an oral BACE-1 inhibitor that has been shown to reduce Aβ levels in the cerebrospinal fluid of healthy people and those affected by Alzheimer's disease by 75%. The researchers in this randomized multicenter pharmaceutical company funded study assessed the safety and efficacy of this investigational drug. The patients were randomized to 12 mg/day group (653), 40 mg/day group (652) and a placebo (653). The trial was terminated early because of the clearly evident futility of the treatment. Verubecestat did not reduce cognitive or functional decline in patients with mild-to- moderate Alzheimer's disease. Moreover, the side effects such as rash, falls and injuries, sleep disturbances, suicidal ideas, weight gain and hair color changes were more common in the verubecestat group. Further trials for establishing the efficacy of BACE-1 inhibitors in the presymptomatic stages of Alzheimer's disease may have a role in the future.

Contributed by Dr. Sahil Mehta

Kunutsor SK, et al. Sauna Bathing Reduces the Risk of Stroke in Finnish Men and Women. a Prospective Cohort Study. Neurology 2018;90:e1937-44.

Sauna bathing has a positive impact on the cardiovascular and the circulatory functions by causing a reduction in the blood pressure, a positive modulation of lipid profiles, a reduction in the arterial stiffness, a reduction in the carotid intima as well as media thickness and a decrease in the peripheral vascular resistance. The authors in this prospective observational study enrolled 1628 participants from Finnish Kuopio ischemic heart disease risk factor study and followed them up for 15 years. They found that participants who had 4-7 bathing sessions per week had lower age and sex adjusted hazard risk for ischemic stroke. Finnish sauna bathing is usually done at temperatures around 80 degrees Celsius compared to the conventional infrared saunas carried out at 60 degree Celsius. These findings suggest that frequent sauna bathing can contribute to the prevention of stroke and cardiovascular events.

Contributed by Dr. Sahil Mehta

Amarenco P, et al . Five- Year Risk of Stroke After Tia or Minor Ischemic Stroke. N Engl J Med 2018;378:2182-90.

The TIA prospectively recruited patients of transient ischemic attack (TIA) or minor stroke through 2009 to 2011 to determine the short term (3 months and 1 year) and the long term (5 year) outcomes. The risk of stroke at 1 year was found to be 5.1% and the presence of multiple infarctions on imaging, large artery atherosclerosis and the age, blood pressure, clinical features, unilateral weakness (ABCD 2) score of 6-7 usually doubled the risk of stroke. The authors now reported the outcomes at 5 years which included 80% of the original cohort. The risk of stroke, acute coronary syndrome or death from cardiovascular causes was 6.4% in the first year as well as over the next four years. Again, the presence of large artery atherosclerosis, cardio-embolism and a higher ABCD 2 score (>4) increased the chance of subsequent stroke. This study provides objective evidences for continuing long-term secondary stroke preventive measures.

Contributed by Dr. Sahil Mehta

Tomson T, et al. Comparative Risk of Major Congenital Malformations With Eight Different Antiepileptic Drugs: a Prospective Cohort Study of the EURAP Registry. Lancet Neurol 2018;17:530-8.

Antiepileptic drugs are known to cause a number of side–effects, an important one of which is teratogenic effect in pregnant women. This article attempts to determine and compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs used as monotherapy. All pregnant female patients who were exposed to antiepileptic drug monotherapy at conception were included from the European registry of antiepileptic drugs and pregnancy (EURAP) with a longitudinal, prospective follow up until 1 year. Carbamazepine, lamotrigine, levatiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate were the drugs included. Of the 7355 pregnancies exposed to these eight antiepileptic drugs, the prevalence of major congenital malformations was the highest (10·3%) for valproate followed by phenobarbital, phenytoin, carbamazepine, topiramate, oxcarbazepine, lamotrigine, and levetiracetam (2·8%), in this order. After dose adjustments, the risk associated with all doses of carbamazepine and valproate was the maximum. These findings reiterate the need for rational selection of antiepileptic drugs, taking into account the comparative risks associated with the various treatment alternatives.

Contributed by Dr. Chirag K Ahuja

Cagnazzo F, et al . Endovascular Treatment of Very Large and Giant Intracranial Aneurysms: Comparison between Reconstructive and Deconstructive Techniques—a Meta-Analysis. Am J Neuroradiol 2018;39:852-8.

Large/giant aneurysms still pose significant safety issues with both reconstructive and deconstructive endovascular treatments. The aim of this study was to compare treatment-related outcomes between these 2 techniques through a systematic search of 3 data bases (1990 to 2017). Appropriate studies with >10 patients each were selected and a random-effects meta-analysis was used to analyze the occlusion rates, complications, and neurologic outcomes. 894 very large/giant aneurysms were included. The long-term occlusion of unruptured aneurysms was 71% and 93% after reconstructive and deconstructive treatments, respectively (P = 0.003). Among the unruptured ones, complications were lower after parent artery occlusion (PAO) (P = 0.05), whereas the complications were lower after reconstructive techniques among the ruptured lesions. PAO in the posterior circulation had higher complications when compared to the anterior circulation. Among the unruptured lesions, the rate of early aneurysm rupture (within 30 days) was slightly higher after reconstructive treatment (P = 0.08) and after flow diversion alone compared with flow diversion plus coiling (7% versus 0%). Thus, PAO allowed high rates of occlusion with an acceptable rate of complications for unruptured, anterior circulation aneurysms. Coiling is preferable for the posterior circulation and ruptured lesions, whereas flow diversion is relatively safe and effective for unruptured anterior circulation aneurysms.

Contributed by Dr. Chirag K Ahuja

Wilson D, et al . Cerebral Microbleeds and Intracranial Haemorrhage Risk in Patients Anticoagulated for Atrial Fibrillation After Acute Ischaemic Stroke or Transient Ischaemic Attack (CROMIS-2): a Multicentre Observational Cohort Study. Lancet Neurol 2018;17:539-47.

Cerebral microbleeds (CMBs), a potential neuroimaging biomarker of cerebral small vessel diseases, were evaluated for their potential role in identifying patients at high risk of symptomatic intracranial haemorrhage (sICH) who were anticoagulated for atrial fibrillation after a recent ischaemic stroke or transient ischaemic attack. Patients from across 80 hospitals in the UK and Netherlands, with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, were recruited in this observational, multicentre, prospective inception cohort study. Of the 1447 participants, sICH rate in patients with CMBs was higher than those without CMBs. It was concluded that in this subgroup of patients, the presence of CMBs was independently associated with a high risk of symptomatic intracranial haemorrhage and could be used for taking informed anticoagulation decisions.

Contributed by Dr. Chirag K Ahuja

Meijerman A, et al . Alzheimer's Disease Neuroimaging Initiative. Reproducibility of Deep Gray Matter Atrophy Rate Measurement in a Large Multicenter Dataset. Am J Neuroradiol 2018;39:46-53.

Volumetric measurements of the grey and white matter are important requisites for an adequate evaluation of various disease states and their response to treatments. A number of softwares are currently available which are capable of this quantitation but variable results still remain a challenge with them. The authors tried to investigate the accuracy and reproducibility of deep gray matter (GM) volumes with two of these softwares using a large multicenter dataset. FreeSurfer and the FMRIB Integrated Registration and Segmentation Tool were evaluated by using back-to-back magnetic resonance (MR) imaging scans from the Alzheimer Disease Neuroimaging Initiative's multicenter dataset. 562 subjects with scans at baseline and 1 year were included. Reproducibility was investigated in bilateral caudate nuclei, putamen, amygdala, globus pallidus, and thalamus. FreeSurfer had a better performance for the outcome of longitudinal volume change for bilateral amygdala, putamen, left caudate nucleus (P< 0.005), and right thalamus (P< 0.001). Further results showed that back-to-back differences in 1-year percentage volume change were approximately 1.5–3.5 times larger than the mean measured 1-year volume change of those structures. It was thus concluded that longitudinal deep GM atrophy measures should be interpreted with caution. Moreover, deep GM atrophy measurement techniques require substantially improved reproducibility, specifically when aiming for personalized medicine.

Contributed by Dr. Chirag K Ahuja

Bruce CV, et al . Tenecteplase Versus Alteplase Before Thrombectomy for Ischemic Stroke. N Engl J Med 2018;378:1573-82.

Bridging therapy involves administration of intravenous alteplase prior to endovascular thrombectomy for ischemic stroke. Tenecteplase is a newer generation drug, which is more fibrin-specific and has a longer activity than alteplase. Randomization was done for the recruited patients (total = 202, 1:1 randomization) to receive either alteplase or tenecteplase after an acute ischemic stroke with occlusion of the internal carotid, basilar, or middle cerebral artery. These recruited patients were eligible to undergo a thrombectomy. The primary outcome (reperfusionof greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment) was seen in more patients with tenecteplase than alteplase (P = 0.03). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin's scale (mRS) 2 vs. 3; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. The authors, thus, conclusively proved the superiority of tenecteplase over alteplase.

Contributed by Dr. Chirag K Ahuja

Al-Ajlan FS, et al . Posttreatment Infarct Volumes When Compared With 24-Hour and 90-Day Clinical Outcomes: Insights from the REVASCAT Randomized Controlled Trial. Am J Neuroradiol 2018;39:107-10.

Endovascular therapy has become the standard of care for patients with acute ischemic stroke. The authors aimed to determine whether the beneficial effect of endovascular treatment on functional outcomes could be explained by a reduction in the posttreatment infarct volume in the Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT) trial. 206 subjects were equally randomized into the endovascular treatment and the control group. Posttreatment infarct volume was measured and compared with the treatment assignment and recanalization status. The median posttreatment infarct volume was significantly lesser in the endovascular treatment arm than the control arm (P = 0.02). While baseline National Institutes of Health Stroke Scale (NIHSS) score, site of occlusion, baseline mormal contrast computed tomographic (NCCT) Alberta Stroke Program Early Computed Tomograpic Score (ASPECTS), and recanalization status were independently associated with posttreatment infarct volume, the baseline NIHSS score, time from symptom onset to randomization, treatment type, and recanalization status were independently associated with the 24-hour NIHSS scores. The 24-hour NIHSS score strongly correlated with the 90-day modified Rankin's scale (mRS) score while posttreatment infarct volumes did not. Thus, it was realized that the endovascular treatment improved 90-day clinical outcomes primarily through a beneficial effect on the 24-hour stroke severity.

Contributed by Dr. Chirag K Ahuja

O'connor EE, et al . Brain Structural Changes Following HIV Infection: Meta-Analysis. Am J Neuroradiol 2018;39:54-62.

HIV is known to cause neurological dysfunction. Many studies have attempted to measure the effects of HIV on the brain macroarchitecture through changes in the total brain volume, gray matter volume, white matter volume, CSF volume, and basal ganglia volume, though the findings are fraught with inconsistencies. The authors evaluated the consistency and temporal stability of sero-status effects on a range of structural neuroimaging measures. The meta-analysis performed by them included 19 cross-sectional studies reporting the HIV effects on the cortical and subcortical volume from 1993 to 2016. Random-effects meta-analysis was used to estimate the individual study standardized mean differences and the study heterogeneity. There was a significant difference of the serological status with respect to reduced total brain volume (P = 0.002), reduced gray matter volume (P = 0.008), reduced white matter volume (P = 0.076) as well as for increased CSF volume (P = 0.001). Basal ganglia volume differences related to sero-status were not significant. Quantitative neurostructural measures can thus reliably detect the effects of HIV infection during treatment, serving as reliable biomarkers of the central nervous system disease.

Contributed by Dr. Chirag K Ahuja

Sadigh G, et al. Radiological Management of Angiographically Negative, Spontaneous Intracranial Subarachnoid Hemorrhage: a Multicenter Study of Utilization and Diagnostic Yield. Neurosurgery

The authors conducted a retrospective multicenter study in which 752 patients of non-traumatic angio-negative subarachnoid haemorrhage (SAH) were included. The patients with intraparenchymal, subdural, or epidural hematomas, in addition to SAH were excluded. The factors studied were 1. utilization rate, 2. diagnostic yield, and 3. median time from admission for the following imaging tests: initial computed tomography angiography (CTA) and digital subtraction angiography (DSA), brain and cervical spine magnetic resonance imaging (MRI), and any repeat DSA or CTA performed either during the initial admission or at the long-term follow-up visit. In 89% of the cases, CTA was performed, and a DSA was performed in all of them. 75% of patients underwent a brain MRI (positive in 0.7% of cases) and 61% underwent a cervical spine MRI (positive in 0.2% of cases). A repeat, same-admission follow-up DSA and CTA were performed in 48% and 51% of patients, out of which 3.3% and 1% were positive, respectively. A delayed follow-up DSA and CTA after discharge were performed in 26% and 7% of patients, and were positive in 2% and 3.7% of cases, respectively. All of these patients had prior negative imaging studies. The authors concluded that brain and cervical spine MRI had a low diagnostic yield while a repeat CTA and DSA had a slightly better yield but were less utilized.

Contributed by Dr. Anant Mehrotra

Jaja BNR, et al . The SAFARI Score to Assess the Risk of Convulsive Seizure during Admission for Aneurysmal Subarachnoid Hemorrhage. Neurosurgery 2018;82:887-93.

The authors developed a score to assess the risk of convulsive seizures during acute admission for subarachnoid haemorrhage (SAH). The score was developed in 1500 patients from a single centre and was externally validated in 852 patients. The SAFARI score, based on 4 items (age ≥60 years, seizure occurrence before hospitalization, ruptured aneurysm in the anterior circulation, and hydrocephalus requiring cerebrospinal fluid diversion), had an area under curve (AUC) of 0.77, and a 95% confidence interval (CI): 0.73-0.82 in the development cohort. The validation cohort had an AUC = 0.65, 95% CI 0.56-0.73. A calibrated increase in the risk of seizure was noted with increasing SAFARI score points. The authors concluded that this score was a simple tool as it utilized readily available factors and it might be able to contribute to a more individualized treatment for seizures in the patients of SAH.

Contributed by Dr. Anant Mehrotra

Wilson MP, et al. Utilizing Pre-Procedural CT Scans to Identify Patients at Risk for Suboptimal External Ventricular Drain Placement With the Freehand Insertion Technique. J Neurosurg 2018 Doi: 10.3171/2018.1.jns172839

The authors retrospectively analysed 189 consecutive adult patients who underwent an external venricular drainage (EVD) placement by a freehand technique. The primary outcome measures included features associated with suboptimal positioning (Kakarla grade 1 vs Kakarla grades 2 and 3). The secondary outcome measures were features associated with unsatisfactory positioning (Kakarla grades 1 and 2 vs Kakarla grade 3). Suboptimal position was seen in 51 of the EVDs (27%). 15 (8%) EVDs were placed into the eloquent cortex or at non-target CSF places. The admitting diagnosis, head height-to-width ratio in the axial plane, and the side of the predominant pathology were found to be significantly associated with a suboptimal EVD placement (P = 0.02, 0.012, and 0.02, respectively). A decreased height-to-width ratio was also associated with the placement into the eloquent cortex and/or the non-target CSF spaces (P = 0.003). The authors concluded that the freehand technique was associated with significant suboptimal positioning of EVDs including penetration into the eloquent cortex. Using baseline clinical and radiographic features, one can predict the likelihood of inaccurate EVD placement.

Contributed by Dr. Anant Mehrotra

Kuo CH, et al. Radiological Adjacent-Segment Degeneration in L4–5 Spondylolisthesis: Comparison between Dynamic Stabilization and Minimally Invasive Transforaminal Lumbar Interbody Fusion. J Neurosurg: Spine Doi: 10.3171/2018.1.spine17993.

The authors conducted a retrospective study on 79 patients with degenerative L4-L5 grade 1 spondylolisthesis. Patients were divided into two groups according to the surgery performed namely: Dynesys dynamic stabilization (DDS) group (n = 56) and the minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) group (n = 23). Pre- and postoperative radiological evaluations, including radiography, computed tomography (CT), and magnetic resonance imaging (MRI) studies, were compared. Adjacent discs were evaluated using 4 radiological parameters: instability (antero- or retrolisthesis), disc degeneration (Pfirrmann classification), endplate degeneration (Modic classification), and range of motion (ROM). Clinical outcomes, measured with the visual analog scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI), and the Japanese Orthopaedic Association (JOA) scores, were also compared. Prior to surgery, both groups were very similar in demographic, radiological, and clinical data. Following surgery, both groups had similarly significant improvement in the clinical outcomes (VAS, ODI, and JOA scores) at each time point of evaluation. There was a lower chance of disc degeneration (Pfirrmann classification) of the adjacent discs in the DDS group than in the MI-TLIF group (17% vs 37%, P = 0.01). However, the DDS and MI-TLIF groups had similar rates of instability (15.2% vs 17.4%, respectively, P = 0.92) and endplate degeneration (1.8% vs 6.5%, P = 0.30) at the cranial (L3–4) and caudal (L5–S1) adjacent levels after surgery. The mean ROM in the cranial and caudal levels was also similar in the two groups. None of the patients required secondary surgery for any ASD (defined by the radiological criteria).

Contributed by Dr. Anant Mehrotra

Creamer M, et al. Intrathecal Baclofen Therapy Versus Conventional Medical Management for Severe Post-Stroke Spasticity: Results from a Multicentre, Randomised, Controlled, Open-Label Trial (SISTERS). J Neurol Neurosurg Psychiatry 2018;89:642-50.

Post stroke spasticity remains a difficult problem to treat. Conventionally, these patients are managed medically, supplemented by physiotherapy and only in those patients who fail to respond adequately is intrathecal baclofen (ITB) advised. Spasticity In Stroke–Randomised Study (SISTERS) was a randomised, controlled, open-label, multicentre phase IV study to evaluate the efficacy and safety of ITB therapy versus conventional medical management (CMM) with oral antispastic medication for the treatment of PSS. Patients with chronic stroke with spasticity involving ≥2 extremities and an Ashworth Scale (AS) score ≥3 in at least two affected muscle groups in the lower extremities (LE) were randomised (1:1) to ITB or CMM. Both the treatment arms received physiotherapy throughout the trial. The primary outcome was the change in the average AS score in the LE of the affected body side from baseline to month 6. Of the 60 patients randomised to ITB (n = 31) or CMM (n = 29), 48 patients (24 per arm) completed the study. The primary analysis showed a significant effect of ITB therapy over CMM although the adverse events of ITB (24/25 patients, 96%; 149 events) were more compared with CMM (22/35, 63%; 77 events).

Contributed by Dr. Kuntal K Das

Pfaff E, et al. Feasibility of Real-Time Molecular Profiling for Patients With Newly Diagnosed Glioblastoma Without MGMT Promoter Hypermethylation-The NCT Neuro Master Match (N2m2) Pilot Study. Neuro Oncol 2018;20:826-37.

The concomitant and adjuvant oral temozolomide, as proposed by Stupp et al., has been a landmark achievement in the management of glioblastomas. However, there is a subset of patients, with the non-hypermethylated O6-methylguanine-DNA methyltransferase (MGMT) enzyme, who do not respond to temozolomide and represent a major management challenge. The current study was an attempt to undertake a comprehensive molecular profiling for this subset of patients in order to plan subsequent targeted studies for MGMT non-hypermethylated GBMs. The authors performed a detailed genetic analysis on 43 subjects of glioblastoma using a host of latest genetic analysis tools like whole-exome sequencing, low-coverage whole-genome sequencing, ribose nucleic acid sequencing, as well as microarray-based gene expression profiling and deoxyribose nucleic acid (DNA) methylation arrays. They found that these battery of tests could fetch results within a reasonable time after surgery. Potentially relevant therapeutic decisions were seen in more than a third of these patients and included alterations in receptor tyrosine kinases; in the members of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin and mitogen-activated protein kinase pathway; as well as in the cell cycle control and p53 regulation cascades. Clonal alterations like oncogenic fusions of tyrosine kinases were also observed. Based on their findings, the authors present an algorithm for these patients with regard to the potentially best treatment option that may be offered to them.

Contributed by Dr. Kuntal K Das

Abdel Hay J, et al. Bupivacaine Field Block With Clonidine for Postoperative Pain Control in Posterior Spine Approaches: a Randomized Double-Blind Trial. Neurosurgery 2018;82:790-8.

The study was conducted to determine the synergistic effect of clonidine in local field block for postoperative analgesia with bupivacaine in the posterior approach to the spine, a procedure otherwise well established in peripheral nerve blocks.

The procedures included a laminectomy, a discectomy as well as fusion of the cervical and the lumbar spine. The patients in each subgroup were randomly divided into a control group (bupivacaine only, n = 109) and clonidine group (n = 116). The area under the curve of pain from postoperative day D0 to D8 and rescue morphine requirements from D0 to D3 constituted the outcome parameters of this study. The authors found the pain reduced in the clonidine group, being statistically significantly for the microdiscectomy subgroup. The total rescue morphine consumption was also lesser in the clonidine group, a benefit that was exclusive for the lumbar stenosis and lumbar fusion subgroups. The field block with clonidine, the surgical subgroup, and the presence of preoperative spinal pain were factors independently influencing postoperative wound pain in the multivariate analysis.

Contributed by Dr. Kuntal K Das and Dr Anant Mehrotra

Brenan PM, et al. Simplifying the Use of Prognostic Information in Traumatic Brain Injury. Part 1: the Gcs-Pupils Score: an Extended Index of Clinical Severity. J Neurosurg 2018:128;1612–20.

It has long been felt that pupillary response of the patients was an important predictor of prognosis after head injury. However, the Glasgow Coma Scale (GCS) has remained the gold standard with its unquestionable utility. Thus, this important paper assumes a great significance, particularly as it comes from none other than the Teasdale group itself. A huge pool of data from two large prospective databases, namely the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9,045) study and the IMPACT (International Mission for Prognosis and Clinical Trials in TBI; n = 6855), were utilized for this purpose. The authors used a simple arithmetic score where the GCS-P score denoted the GCS score [range 3–15] minus the number of non-reacting pupils (0, 1, or 2). The composite score thus ranged from 1-15. The authors found this score comparable to other similar scores, which were more complex in computation. The relationship between decreases in the GCS-P and deteriorating outcome was seen across the complete range of possible scores. This new score provided two new scores (GCS-P 1 and 2), not available in the original GCS score. The analysis found that GCS-P 1 was associated with 90% chances of an unfavorable outcome as against 70% chance predicted by the conventional GCS score.

Contributed by Dr. Kuntal K Das

Shin SM, et al. Clinical Effectiveness of Intra-Articular Pulsed Radiofrequency Compared to Intra-Articular Corticosteroid Injection for Management of Atlanto-Occipital Joint Pain: a Prospective Randomized Controlled Pilot Study. Spine (Phila Pa 1976). 2018;43:741-6.

This was a prospective randomized pilot study to assess the effectiveness of pulsed radiofrequency (PRF) ablation against the well proven procedure of intraarticular (IA) corticosteroid injection of the atlanto-occipital (AO) joint in patients with chronic joint pain. The authors randomized twenty-three consecutive patients with chronic upper cervical pain into the two groups (12 patients in the PRF group and 11 patients in the IA corticosteroid injection group). Both the patient groups showed a significant improvement in their pretreatment pain intensity on the numeric rating scale (NRS) although the temporal changes at various time points at follow-up did not differ significantly. The proportion of successful pain relief was better in the PRF group (66.7% vs 63.6%).

Contributed by Dr. Kuntal K Das


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