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Table of Contents    
NI FEATURE: THE FOURTH DIMENSION - COMMENTARY
Year : 2018  |  Volume : 66  |  Issue : 5  |  Page : 1453-1468

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


1 Department of Neurosurgery, Wockhardt Hospital and Grant Medical College, Mumbai, Maharashtra, India
2 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, Karnataka, India
3 Department of Radiology, Postgraduate Institute of Medical Education and Research, Chandigarh, Karnataka, India
4 Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, Karnataka, India
5 Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
6 Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication17-Sep-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: 10.4103/0028-3886.241395

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How to cite this article:
Turel MK, Tripathi M, Aggarwal A, Ahuja CK, Takkar A, Mehta S, Yadav R, Mehrotra A, Das KK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India 2018;66:1453-68

How to cite this URL:
Turel MK, Tripathi M, Aggarwal A, Ahuja CK, Takkar A, Mehta S, 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 Oct 23];66:1453-68. Available from: http://www.neurologyindia.com/text.asp?2018/66/5/1453/241395




Chiba K, et al. Condoliase for the treatment of lumbar disc herniation: A randomized controlled trial. Spine (Phila Pa 1976) 2018:1;43:E869-E76.

Condoliase is a pure mucopolysaccharidase derived from a bacterium, Proteus vulgaris, that has a high substrate specificity for chondroitin sulfate and hyaluronic acid in the nucleus pulposus of the intervertebral disc. In this study, patients aged 20 to 70 years with unilateral leg pain, positive straight leg raising test, and contained lumbar disc herniation (LDH) were treated with a single injection of intradiscal condoliase (1.25U) or a placebo, and were followed for 1 year after administration of the injection. The primary endpoint was a change in the worst leg pain from the baseline until week 13. A total of 82 and 81 patients received an injection of condoliase and a placebo, respectively. The average changes in the worst leg pain from the baseline until week 13 (the primary endpoint) were 4.9 in the condoliase group and 3.4 in the placebo group, with this difference being significant. Significant improvements were observed in the condoliase group compared with the placebo group, in most secondary endpoints such as Oswestry Disability Index, 36-item Short-Form Health Survey, neurologic examinations, and imaging parameters at 1 year after administration of the injection. In the condoliase group, back pain, Modic type 1 change, and decrease in the disc height were frequently reported, without any clinically relevant consequences. The study concluded that condoliase significantly improved symptoms in patients with LDH and was well tolerated.

Contributed by Dr. Mazda K. Turel

Park S, et al. How many screws are necessary to be considered an experienced surgeon for freehand placement of thoracolumbar pedicle screws? Analysis of the learning curve using the cumulative summation test for learning curve (LC-CUSUM). World Neurosurg 2018 doi: 10.1016/j.wneu. 2018.06.236.

This study included the first 85 patients who underwent pedicle screw placement in the thoracic and lumbar spine by a single orthopedic surgeon. The surgeon had one year's experience of fellowship training in the tertiary teaching hospital. The learning curve of freehand pedicle screw placement (PSP) was investigated using a specialised analysis. The ‘procedure success' was defined as an acceptable accuracy of pedicle screw placement, which was divided into two groups (group 1: The screw breached the pedicle's cortex by less than 2 mm; and, group 2: The screw was completely within the pedicle). A total of 52 cases in whom 313 pedicle screws were placed, were included and analyzed in this study. The analysis signalled the development of competency for freehand PSP at the 115th pedicle screw (17th case) in group 1, and at the 312th pedicle screw (52nd case) in group 2. This means that a trainee with no experience with freehand PSP reached an adequate accuracy level of pedicle screw placement with less than 2mm pedicle breach at the 115th screw that he placed; on the other hand, the pedicle screw was completely within the pedicle at the 312th screw placement. There were no major complications, such as neurovascular injury, or any other life-threatening complications. In this study, the learning curve analysis demonstrated that a substantial learning period may be necessary before an adequate level of performance is achieved for freehand PSP in the non-deformed thoracolumbar spine.

Contributed by Dr. Mazda K. Turel

Deletis V, et al. Intraoperative identification of the corticospinal tract and the dorsal column of the spinal cord by electrical stimulation. J Neurol Neurosurg Psychiatry 2018;89:754-61.

Anatomical identification of the corticospinal tract (CT) and the dorsal column (DC) of the exposed spinal cord is difficult when anatomical landmarks are distorted by tumour growth. Neurophysiological identification is complicated by the fact that direct stimulation of the DC may result in muscle motor responses due to the centrally activated H-reflex. This study aimed to provide a technique for intraoperative neurophysiological differentiation between CT and DC in the exposed spinal cord in 32 consecutive patients undergoing spinal cord tumour surgery. A double train stimulation paradigm with an intertrain interval of 60 ms was devised with recording of responses from limb muscles. In non-spastic patients (55% of cohort), an identical second response was noted following the first CT response, but the second response was absent after DC stimulation. In patients with pre-existing spasticity (45%), CT stimulation again resulted in two identical responses, whereas DC stimulation generated a second response that differed substantially from the first one. The recovery times of interneurons in the spinal cord grey matter were much shorter for the CT than those for the DC. Therefore, when a second stimulus train was applied 60 ms after the first, the CT-fibre interneurons had already recovered ready to generate a second response, whereas the DC interneurons were still in the refractory period. Thus, mapping of the spinal cord using double train stimulation allows neurophysiological distinction of CT from DC pathways during spinal cord surgery in patients with and without pre-existing spasticity.

Contributed by Dr. Mazda K. Turel

Tang B, et al. Which is the better timing between embolization and surgery for hypervascular spinal tumors, the same day or the next day? A retrospective comparative study. Medicine (Baltimore) 2018;97:e10912

The aim of this study was to determine the better timing (the same day or the next day) between embolization and surgery for hypervascular spinal tumors by assessing the safety and efficacy of embolization. The time between embolization and surgery was mainly determined by the schedules of the interventional radiologist as well as the operating room available. Of the 125 embolizations, there were 4 major complications, all of which occurred on the same day of the procedure. Of the 120 operations, 36 cases were operated on the same day of embolization, 74 on the next day, and 10 on the second day. When comparing the efficacy of embolization between the same day and the next day group, the intraoperative blood loss (1483 mL vs 1548 mL), the intraoperative transfusion requirement (1011 mL vs 1112 mL), and the postoperative blood loss (1146 mL vs 1031 mL) were not significantly different. Embolization carried a certain risk (4/125, 3.2%) of major complications, which may have occurred within the time window of a day. Based on these findings, the authors suggest that the operation should be scheduled on the next day of embolization, if possible.

Contributed by Dr. Mazda K. Turel

Bates A, et al. Primary and metastatic brain tumours in adults: Summary of NICE guidance. BMJ 2018:362;k2924.

This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on the management of glioma, meningioma, and cerebral metastases. It particularly focuses on recommendations about the longer term follow-up of patients and potential complications of treatment. While it is definitely recommended to read the entire guidelines, presented here are some key changes. It is recommended not to offer tumour-treating fields (continuous application of electrical fields to the scalp) as they are not cost-effective under the conventional criteria. Irradiation of the surgical cavity is recommended after resection of 1-3 brain metastases. 5-Aminolevulinicacid (5-ALA) is recommended to help in improving the resection if the multidisciplinary team thinks that surgical resection of all enhancing glioma is possible–this is likely to have a high cost impact on neurosurgical units. The paper has also suggested follow up schedules for each grade of glioma and meningioma to maintain uniformity in protocol across the the country for research and clinical practice.

Contributed by Dr. Mazda K. Turel

Shi Y, et al. Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance. Sci Transl Med 2018;10(443) doi: 10.1126/scitranslmed.aah6816.

Glioblastoma is a lethal and difficult-to-treat primary brain tumor. Similar to many cancers, glioblastoma contains a population of stem cells, which are particularly treatment-resistant and promote tumor growth. A protein called bone marrow and X-linked (BMX) nonreceptor tyrosine kinase is active in these cells and can be targeted with ibrutinib, an approved drug used in other cancers such as lymphomas and leukemias. The authors demonstrated that ibrutinib specifically targets glioma stem cells but not healthy neural stem cells, which do not express BMX. The authors demonstrated the effectiveness and safety of ibrutinib treatment in mouse models.

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 the histological features routinely used in clinical practice 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 molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations that are based on glioblastoma pathogenesis, diagnosis, and treatment. It is aimed at helping researchers and physicians in improving the diagnosis and treatment of a glioblastoma, including the finding of new drug targets.

Contributed by Dr. Mazda K. Turel

Souweidane MM, et al. Convection-enhanced delivery for diffuse intrinsic pontine glioma: A single-centre, dose-escalation, phase 1 trial. Lancet Oncol 2018 doi: 10.1016/S1470-2045(18)30322-X.

The authors did a phase 1, single-arm, single-centre, dose-escalation study at the Memorial Sloan Kettering Cancer Center to evaluate the safety of convection-enhanced delivery of a radio- immunotherapeutic agent targeting the glioma-associated B7-H3 antigen in children with diffuse intrinsic pontine glioma. One (4%) of 28 patients had treatment-related transient grade 3 hemiparesis and one (4%) had grade 3 skin infection. No treatment-related grade 4 adverse events or deaths occurred. The authors concluded that convection-enhanced delivery of a radio- immunotherapeutic agent in the brainstem of children with diffuse intrinsic pontine glioma, who have previously received radiation therapy, seems to be a rational and safe therapeutic strategy. Positron emission tomography-based dosimetry of the radiolabelled antibody [124I]-8H9 validated the principle of using convection-enhanced delivery of the agent in the brain to achieve high intra-lesional dosing with negligible systemic exposure. This therapeutic strategy warrants further development for use in children with diffuse intrinsic pontine glioma.

Contributed by Dr. Mazda K. Turel

Volkers EJ, et al. Prediction models for clinical outcome after a carotid revascularization procedure: An external validation study. Stroke 2018 doi: 10.1161/STROKEAHA.117.020486.

From a literature review, the authors selected all of those prediction models that used only readily available patient characteristics known before the revascularization procedure initiation. The follow-up data from 2184 patients undergoing carotid artery stenting and 2261 patients undergoing carotid endarterectomy from 4 randomized trials (EVA-3S [Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis], SPACE [Stent-Protected Angioplasty Versus Carotid Endarterectomy], ICSS [International Carotid Stenting Study], and CREST [Carotid Revascularization Endarterectomy Versus Stenting Trial]) were used to validate 23 short-term outcome models to estimate stroke- or death-risk ≤30 days after the procedure. Stroke or death ≤30 days after the procedure occurred in 158 (7.2%) patients after carotid artery stenting and in 84 (3.7%) patients after carotid endarterectomy. Most models for determining the short-term outcome had a poor discriminative performance and poor calibration with small absolute risk differences between the lowest and highest risk groups, and overestimation of the risk in the highest risk groups. Long-term outcome models had a slightly better performance. The authors concluded that current models did not reliably predict outcome after carotid revascularization. In particular, prediction of short-term outcome seemed to be difficult.

Contributed by Dr. Mazda K. Turel

Zijlmans JL, et al. Unfavourable outcome in patients with aneurysmal subarachnoid haemorrhage WFNS grade I. World Neurosurg 2018 doi: 10.1016/j.wneu. 2018.06.157.

Patients who have suffered an aneurysmal subarachnoid haemorrhage (aSAH) and are in the World Federation of Neurosurgical Societies (WFNS) grade I at admission are generally considered to have a good clinical outcome. The objective of this study was to assess the actual clinical outcome of 132 consecutive WFNS grade I aSAH patients, and to determine the factors that were associated with an unfavourable outcome. The clinical outcome was measured using the modified Rankin Scale (mRS) at a six month follow-up. Unfavourable outcome was defined as an mRS score of 3-6. Of 116 patients with the available follow up, only five (4%) had an mRS score of 0 and most (65%) had an mRS score of 2. Twenty-five (22%) patients had an unfavourable outcome. Nine (8%) patients died, of whom four patients expired during their admission. Factors associated with an unfavourable outcome were the age of the patients per increasing decade, delayed cerebral ischemia, pneumonia and meningitis. The conclusion of this study from the Netherlands is that despite their neurologically optimal clinical condition on admission, one out of five WFNS grade I aSAH patients has an unfavourable clinical outcome, or is dead, when the cohort is assessed at a follow-up of 6 months.

Contributed by Dr. Mazda K. Turel

Hilkens NA, et al. Predicting the presence of macrovascular causes in non-traumatic intracerebral haemorrhage: The DIAGRAM prediction score. J Neurol Neurosurg Psychiatry 2018;89:674-9.

The role of imaging in the detection of an underlying structural or macrovascular cause of acute intracerebral haemorrhage (ICH) is poorly defined. The DIagnostic AngioGRAphy to find vascular Malformations (DIAGRAM) study (n = 298; 69 macrovascular cause; 23%) was a prospective, multicentre study assessing the yield and accuracy of CT angiography (CTA), magnetic resonance imaging [MRI]/magnetic resonance angiography (MRA) and intra-arterial catheter angiography in diagnosing macrovascular causes in patients with non-traumatic ICH. The authors introduce a simple individualised decision-making tool (age <50 vs ≥50–70 years, lobar/posterior fossa vs deep location, presence vs absence of small vessel disease (SVD) on the CT scan, or the presence of positive (or uncertain) vs negative findings on CT angiography [CTA]) that shows a high predictive ability for detecting an underlying macrovascular cause of acute ICH.

Contributed by Dr. Mazda K. Turel and Dr. Chirag K. Ahuja

Trevisi G, et al. What is the best timing of repeated CT scan in mild head trauma with an initial positive CT scan? World Neurosurg 2018 doi: 10.1016/j.wneu. 2018.06.185.

The authors retrospectively analysed 222 patients admitted after a mild traumatic brain injury (MTBI) and a positive initial scan. Repeated CT scans were categorized according to timing from the first scan. They classified data in 3 groups based on the timing (in hours) of CT scans: A (CT scans at t0-t12-t24), B (t0-t12-t48), C (t0-t24-t48). 146 CT scans were performed at t12, 81 at t24, and 143 at t48. The initial CT scan was positive for an epidural hematoma in 17, a subdural hematoma in 106, a subdural hygroma in 10, an intracerebral contusion in 110, a subarachnoid hemorrhage in 109, and an intraventricular hemorrhage in 12 patients. None of the post-traumatic lesions showed a significant worsening in the first or second CT scan in any of the 3 groups. Thus, it was concluded that based on the neurological stability, a control scan can be safely delayed up to 48 hours in order to avoid the performance of unnecessary CT scans.

Contributed by Dr. Mazda K. Turel

Blomstedt P, et al. Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: A randomised blinded evaluation. J Neurol Neurosurg Psychiatry 2018;89:710-6.

Several open-label studies have shown the good effect of deep brain stimulation (DBS) in the caudal zona incerta (cZi) on tremor, including parkinsonian tremor, and in some cases, also a beneficial effect on akinesia and axial symptoms. The aim of this study was to evaluate objectively the effect of cZi DBS in patients with Parkinson's disease (PD). 25 patients with PD were randomised to either cZi DBS or best medical treatment. The primary outcomes were the differences obtained between the groups in the motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS-III), rated single-blindly at 6 months, and differences in the Parkinson's Disease Questionnaire 39 items (PDQ-39). 19 patients, 10 in the medical arm and 9 in the DBS arm, fulfilled the study. The DBS group had 41% better UPDRS-III scores off-medication on-stimulation compared with baseline, whereas the scores of the non-surgical patients off-medication remained unchanged. In the on-medication condition, there were no differences between the groups, neither at baseline nor at 6 months. Sub items of the UPDRS-III showed a robust effect of cZi DBS on tremor. The PDQ-39 domains ‘stigma' and ‘activities of daily leaving [ADL]' improved only in the DBS group. The PDQ-39 summary index improved in both the groups. This was the first randomised blinded evaluation of cZi DBS showing its efficacy on the symptoms of PD. The most striking effect was on tremor; however, the doses of dopaminergic medications could not be decreased. cZi DBS in PD may be an addition to the existing established targets, enabling tailoring of the surgery to the needs of the individual patient.

Contributed by Dr. Mazda K. Turel

Ho AL, et al. Awake versus asleep deep brain stimulation for Parkinson's disease: A critical comparison and meta-analysis. J Neurol Neurosurg Psychiatry 2018;89:687-91.

The authors conducted a literature review and meta-analysis of all published studies on deep brain stimulation (DBS) for Parkinson's disease [PD] (n = 2563) available on PubMed from January 2004 to November 2015. There was no significant difference in the mean target error between local and general anaesthesia, but there was a significantly lesser mean number of DBS lead passes with general anaesthesia. There were also significant decreases in DBS complications, with fewer intracerebral haemorrhages and infections with general anaesthesia. There were no significant differences in Unified Parkinson's Disease Rating Scale (UPDRS) Section II scores off medication, UPDRS III scores off and on medication, or levodopa equivalent doses between the two techniques. Awake DBS cohorts had a significantly greater decrease in treatment-related side effects, as measured by the UPDRS IV off medication score (78.4% awake vs 59.7% asleep, P = 0.02). The meta-analysis demonstrated that while DBS under general anaesthesia may lead to the occurrence of lower complication rates overall, awake DBS may lead to less treatment-induced side effects. Nevertheless, there were no significant differences in the clinical motor outcomes between the two techniques. Thus, DBS under general anaesthesia can be considered at experienced centres in patients who are not candidates for traditional awake DBS, or in those patients who prefer the asleep alternative.

Contributed by Dr. Mazda K. Turel

Malcolm JG, et al. Early cranioplasty is associated with greater neurological improvement: A systematic review and meta-analysis. Neurosurgery 2018;82:278-88.

The optimal timing of cranioplasty has not been well established. The authors conducted a systematic review to investigate if the timing of cranioplasty is associated with differences in neurological outcome. Pre- and post-cranioplasty neurological assessments for cranioplasty performed within (early) and beyond (late) 90 d were extracted. Eight retrospective observational studies were assessed that included a total of 528 patients. Cranioplasty, regardless of the timing, was associated with a significant neurological improvement. Comparing early and late cohorts, there was no difference in the pre-cranioplasty neurological baseline; however, the post-cranioplasty neurological outcome showed a significantly improved result in the ‘early cranioplasty' cohort and also showed greater magnitude of change of neurological status.

Contributed by Dr. Mazda K. Turel

Lee KS, et al. Cerebral aneurysms in judicial precedents. J Korean Neurosurg Soc 2018;61:474-7.

Neurosurgery is one of the most adversely affected branches in terms of the litigations instituted against doctors among all the branches in medical practice. In USA, nearly 20% of the neurosurgeons face a malpractice claim annually. Aneurysmal subarachnoid haemorrhage (SAH) is one of the most dramatic events in neurosurgical practices as the stakes remain high and confounding variables such as vasospasm may entirely change the prognosis of the patients despite of the performance of an excellent surgical intervention. In the times of dwindling trust on health care, and the consumeristic attitude of patients, one frequently finds onself in similar situation as Pilot Sully found himself after successfully landing a plane on the Hudson river in the “Miracle on the Hudson” episode (beautifully directed by Clint Eastwood in Hollywood movie “Sully”). In this controversial law, Korean government announced automatic mediation without the agreement of the defendant, if the patient suffers an adverse outcome. The most common cited reasons for litigation were failure to diagnose or treat the condition in a timely fashion. The onus of responsibility is different and is based on whether the primary evaluating physician is an internist or an expert. In the majority of cases, the timing of intervention had been left to the discretion of the expert.

This article generates many important implications. Such litigations are going to increase the practice of “defensive medicine”, which will not be in the favour of patient or the growth of neurosurgical training. Secondly, the practice of automatic mediation should be discouraged as it may start the practice of blackmailing in routine clinical care. Doctors should be trained in their curriculum to deal with medico-legal issues, as these issues would be the norm in the wake of changing moral standards of the society and the pressures from the insurance companies. Atul Gawande in his book “Better” has highlighted that most of the lawyers arguing in support of such cases are trained doctors from the plaintiff's side. The jury needs expert, unbiased, witnesses so that no party faces harm; and undue harassment, that may actually lead to the termination of careers and compromise the bright futures of some of the doctors, may be avoided.

Contributed by Dr. Manjul Tripathi

Truog RD, et al. The 50-year legacy of the Harvard report on brain death. JAMA 2018.

In present times, discussion of death has become more fascinating than life. 2018 is the golden jubilee year of the first submission of brain death report by the Beecher committee of Harvard Medical School. The primary purpose of this committee was to “define irreversible coma as a new criterion for death”. The debate about brain death got further fueled with the introduction of ventilators and organ transplantation, which led to an increase in the number of comatose patients with a beating heart. The committee also faced criticism, as the primary motive of declaring brain death was not clear: Was it to decrease the burden on families, of prolonging life of a patient suffering from an irreversible brain damage; or, was it to formulate a policy that was supportive of harvesting organs for organ transplantation. The confusion was so much that different states of USA adopted their own version of the criteria of brain death that had the consequence of labelling the same patient as dead in one state and alive in the other. In 1981, the President's commission formulated a uniform criteria to end this confusion. Declaration of brain death is a moral and legal responsibility of the physician. The greatest influence of a properly implemented critera is on those patients who are in dire need of organs to save their lives. Each year, nearly 8000 donors are declared brain dead as per the neurological criteria, and every donor can benefit at least 8 lives.

Death is perhaps the most emotional moment for a patient's family. Explaining scientific death and fitting it into societal death are two different things. With advancements in medical science, the integrated body function can be maintained for decades with supportive care, but this life is hardly worth living. Even after five decades of proposing the definition of brain death, the subject still generates controversy. The definition remains settled but the implications are often disputed.

Contributed by Dr. Manjul Tripathi

Desjardins A, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Eng J Med 2018. doi: 10.1056/NEJMoa1716435.

In a new attempt to fight glioblastoma multiformae, the authors have tried to attack the poliovirus CD155 receptor with convection enhanced, intratumoral delivery of the recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO). 61 patients of recurrent GBM received seven doses first in the dose escalation pattern, and then in the dose enhancement pattern. Despite the long term need for administration of glucocorticoids/bevacizumab with this therapy and the potential for the occasional precipitation of intracranial hemorrhage, this therapy was helpful in providing a longer survival in the range of 24-36 months than was determined among the historical controls. None of the patients developed any neurovirulence by the virus or any treatment related adverse event (except in one patient who developed an intracerebral hematoma). Few patients have had a longevity beyond 69 months since they underwent treatment. The authors have provided a safe dose profile, derived from the results of this study, and the phase two trial is underway with concurrent administration of lomustine. Intratumoral infusion of PVSRIPO in patients with recurrent World Health Organisation grade IV malignant glioma confirmed the absence of the neurovirulent potential of the method. Interestingly, the survival rate among patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the survival rate detectable among historical controls.

Contributed by Dr. Manjul Tripathi, Dr. Aastha Takkar and Dr. Kuntal K. Das

Heidelberger D, et al. Essential tremor. N Eng J Med 2018;378:1802-10.

This clinical vignette by Haubenberger et al., is a beautiful and a concise piece of the current evidence available on the evaluation, diagnosis, and management options in essential tremors. The new working diagnosis by the ‘International Parkinson's and Movement Disorder Society (2017)” clearly defines ‘essential tremor' and ‘essential tremor plus' as two separate clinical conditions. ET should now be considered as a neurodegenerative disease. This fact is supported by concrete evidence of a familial pattern of inheritance of variable expression, and the biochemical/autopsy findings that are suggestive of cerebellar dysfunction in these patients. However, there are several caveats, which remain unanswered. There is no precise definition of what constitutes an adequate medical management akin to Parkinson's disease. Propanolol and primidone are still considered the medications that are used in the first line of management of essential tremors; yet their long term efficacy gets blunted either because of the development of tolerance or of side effects over the course of time. An unilateral thalamotomy is a good option in resource stricken countries but performance of bilateral thalamotomies is associated with the significant side effects of dysarthria, and gait disturbance. The US Food and Drug Association (US FDA) has approved of the magnetic resonance-guided, focused ultrasound therapy for the lesion generation, which has good short-term effects. The long-term studies are still warranted, and this methodology of management is approved only for ET among all the other movement disorders. DBS is the preferred modality because of a; the ability to perform bilateral stimulation, b, its reversibility; c, the possibility of performing sham surgeries; d, its adaptability and titratability. However, DBS also suffers from the possibility of developing tolerance on the long-term basis. What remains undefined are the definitions of “cure” and “remission”. While we have come a long way, the cure is still not in sight.

Contributed by Dr. Manjul Tripathi

Wade RG, et al. Absorbable versus non-absorbable sutures for skin closure after carpal tunnel decompression surgery. Cochrane Database Syst Rev 2018. DOI: 10.1002/14651858.CD011757.pub2.

Carpal tunnel decompression is a commonly performed surgery for median nerve decompression at the wrist. Though the surgery is minor, there is an incision of the size of nearly an inch over the palm. There is no consensus guideline for the closure of this incision by either absorbable or non-absorbable suture. In this Cochrane review, the authors have tried to evaluate the level of evidence in support of or against the use of an absorbable suture or a non-absorbable suture for the skin closure after performance of surgery for carpal tunnel syndrome. Surprisingly, it could not be ascertained whether or not absorbable sutures confer better, worse or equivalent outcomes compared to non-absorbable sutures, following the decompression. The only definite benefit is in the elimination of the need for suture removal, which could confer a financial burden on the patient and the health care providers. The very low quality of evidence contributing to this analysis demands further studies that concentrate on the post-operative scar formation, wound infection, hand function, and the patients' level of satisfaction. These conclusions are applicable to both open and endoscopic carpal tunnel decompressions.

Contributed by Dr. Manjul Tripathi

Miguel EC, et al. Evolution of gamma knife capsulotomy for intractable obsessive compulsive disorder. Mol Psychiatry 2018. DOI 10.1038/s41380-018-0054-0.

Obsessive compulsive disorder (OCD) is a poorly recognized and managed psychiatric problem. In the Western literature, the lifetime risk of developing OCD in the general population is 3%, out of which it remains refractory to the medical management in around 20% cases. A neurosurgical stereotactic lesioning often remains the only hope for nearly 1% of the resistant cases of OCD. The target location for radiosurgical lesioning has now shifted from the gamma ventral capsulotomy to the ventral subregion within the anterior limb of internal capsule (ALIC). This article should be applauded for its concise but comprehensive review of the epidemiology, pathophysiology, target locations, and comparative treatment analysis of OCD. The established criteria at present is the Yale Brown Obsessive Compulsive Scale (Y-BOCS), and a full treatment score is considered as 35% decrease in the score. However, there are several challenges that lead to an uncertain outcome in the published literature. The dose has been reduced from the earlier value of 200 Gy to 140 Gy in the recent publications. This has definitely reduced the incidence of side effects but the time-to- obtain-clinical effect has increased. Most of the cases start showing improvement only after 6-12 months of gamma knife radiosurgery. There is no sham effect, as proven by a prominent radiosurgeon. Patients with hoarding effects are prone to developing a poor response to both conventional and radiosurgical treatment. Although there is some evidence that neuro-imaging characteristics of the brain prognosticate the outcome after GKC, any concrete evidence in support of this fact is far from reality. An important technical advice by Ian Paddick is to use a triple shot with prolate geometry to minimize dose delivery to the normal brain parenchyma in medial-lateral direction. In the absence of any level one evidence of superiority of one study over another, different treatment modalities will be practiced based upon the local needs, experience and availability of treatment modalities, as well as the patient's choice.

Contributed by Dr. Manjul Tripathi

Chan MD, et al. Atypical meningioma: An evolving landscape and moving target. Int J Rad Onco 2018. don: 10.1016/j.ijrobp.2018.02.027.

This beautiful commentary on atypical meningiomas highlights the frustrations of the treating neurosurgeons and radiation oncologists in dealing with this entity. This article is a critical analysis of the best evidence obtained from three leading international trials on atypical meningiomas. Contrary to the findings in gliomas, the molecular analysis in grade 2 meningiomas are not able to predict the clinical behaviour or guide the treatment options of these tumors. The Radiation Therapy Oncology Group (RTOG) 0539 and European Organisation for Research and Treatment of Cancer (EORTC) 26042 trials were prospective trials with the longest follow up of three-year duration. In the absence of a longer term follow up assessing the indolent nature of the disease, it would be interesting to see if the improved local control translates into improved overall survival of all these patients. The South-West Oncology Group (SWOG) 9005 trial was a landmark study as it questioned the efficacy of mifepristone as a chemotherapeutic agent. Progesterone receptors are expressed in more than 70% of meningiomas, but this trial showed no significant survival advantage in these patients. However, this finding needs further validation because of some inclusion irregularities and a long interval between the trial and its publication. Sahm et al., attempted the sub-classification of meningiomas on the basis of their deoxyribose nucleic acid [DNA] methylation status and genetic mutations. Similar to the World Health Organization grading system, the methylation classes more accurately identified patients with grade 1 tumors that were at a high risk of progression, and also the grade 2 tumors that were associated with a lower recurrence risk. With adjuvant radiosurgery, the 10-year tumor control rate for grade 1, 2, and 3 meningiomas remained 90%, 50%, and 11%. Hence, the management of atypical meningiomas still remains nebulous as the complication profile of radiation therapy is not trivial enough to justify its administration in every case following total excision of these lesions, and the management options in a cognitively challenged patient still remain extremely limited.

Contributed by Dr. Manjul Tripathi

Gu J, et al. Hypertonic saline or mannitol for treating elevated intracranial pressure in traumatic brain injury: A meta-analysis of randomized controlled trials. Neurosurg Rev 2018. doi: 10.1007/s10143-018-0991-8.

There is no doubt that hyperosmolar therapy continues to be one of the cornerstones of medical management of raised intracranial pressure. The debate regarding whether mannitol or hypertonic saline (HS) is better in controlling raised intracranial pressure (ICP) continues. The authors, in the present study, did a meta-analysis of previous studies to understand the relative merits and demerits of mannitol and HS in raised intracranial pressure secondary to traumatic brain injury. They analyzed 12 studies with a patient number of 438. The analysis revealed that HS was more efficacious than mannitol in decreasing ICP though this was statistically not significant. At the same time, disturbances in serum sodium and serum osmolality were also more with HS. There was no difference in mortality and neurological functional outcome between the two groups. Finally, the authors do not give a specific recommendation of one over the other as the first line management strategy for treating raised ICP. In refractory raised ICP, HS seems to have some edge.

Contributed by Dr. Ashish Aggarwal

Yao A, et al. Can MRI predict meningioma consistency? A correlation with tumor pathology and systematic review. Neurosurg Rev 2018;41:745-53.

A soft/suckable meningioma tends to have a better surgical outcome in terms of completeness of excision and fewer complication rates. This helps in better disease prognostication. The authors studied the characteristics of the preoperative magnetic resonance imaging (MRI) that predicted the tumor consistency and expected histology. This was a systematic review of 21 previous studies. The analysis revealed that tumors which were hyperintense (relative to cerebral cortex) on T2 weighted images were soft in consistency. The T1 weighted image alone failed in predicting consistency. However, if the tumor was T1 hypointense in addition to T2 hyperintense, the predictability increases. An important point was to quantitatively calculate the signal intensity of the tumor and cerebral cortex rather than simply stating that the tumor is hyper- or hypointense. Regarding the prediction of histology, tumors hyperintense on T2 had a higher chance of having cellular atypia, invasion, angioblastic, or melanocytic components, while hypointense tumors (on T2 weighted images) were mostly fibroblastic. To further characterize the tumors, advanced MRI techniques such as magnetic resonance elastography (MRE) and fractional anisotrophy (FA) may prove useful.

Contributed by Dr. Ashish Aggarwal

Esquenazi Y, et al. Thalamic glioblastoma: Clinical presentation, management strategies, and outcomes. Neurosurgery 2018;83:7685.

This retrospective study was conducted on fifty-seven patients (31 men and 26 women) suffering from a thalamic glioblastoma. Their age ranged from 18 to 83 years (with the median age being 53 years). The authors collected clinical, radiological, and outcome data. Thalamic tumors are rare, deep-seated, situated at an eloquent location, making them non- amenable to complete surgical excision. Therefore, the goal of adequate cytoreduction is not achieved. The patients in the present study were subjected to either stereotactic biopsy, or craniotomy and subtotal tumor excision. Even in this seemingly non-radical surgery, immediate postoperative surgical complications occurred in 9 (16%) patients. A younger age and a higher Karnofsky performance scale (>80) were regarded as a good prognostic criteria. Involvement of the midbrain was not considered as a bad prognostic sign. The authors summarize that biopsy followed by adjuvant therapy appears to be the management option at present. They even state that empiric therapy in the absence of tissue diagnosis is also not unreasonable.

Contributed by Dr. Ashish Aggarwal

Nav Lv, et al. Relationship between aneurysm wall enhancement in vessel wall magnetic resonance imaging and rupture risk of unruptured intracranial aneurysms. Neurosurgery 2018. don: https://doi.org/10.1093/neuros/nyy310.

A vascular neurosurgeon faces the dilemma of operating/not operating on an unruptured intracranial aneurysm (UIA). Is there an objective way to predict which of these aneurysms will rupture? The authors in the present study compared the aneurysm wall enhancement (AWE) on vessel wall magnetic resonance imaging (VW-MRI) with the PHASES score (that includes the population, hypertension, age of the patient, size of the aneurysm, the history of an earlier subarachnoid hemorrhage from another aneurysm and the site of the aneurysm) to assess the risk of rupture. This was a retrospective study on 110 patients harboring 140 aneurysms. The study found that AWE was associated with an unfavourable aneurysm size, shape and location, leading to more chances of rupture. The higher rupture risk score with AWE correlated with a higher rupture risk on the PHASES score. This method can potentially be a useful tool to guide the treatment for UIA.

Contributed by Dr. Ashish Aggarwal

Texakalidis P, et al. Impact of powdered vancomycin on preventing surgical site infections in neurosurgery: A systematic review and meta-analysis. Neurosurgery 2018. doi: 10.1093/neuros/nyy288.

Surgical site infection (SSI) after spinal and/or cranial surgery can potentially occur in upto 12% patients. This is a major cause of morbidity and mortality. The authors did a meta-analysis of a novel method –instillation of powdered vancomycin within the wound to prevent SSIs. A total of 31 previously published studies were analyzed involving 18,146 patients. Vancomycin was given in a dose varying between 0.5 g and 2 g. After spinal surgery, 1.9% of the patients of the vancomycin group (VG) and 4.3% of the patients of the non-VG (NVG) group had SSI. Importantly, this protection was for deep SSIs (involving the sub-fascial tissues and/or the spinal implant) but not for superficial SSIs. For cranial surgery, the rates of infection were 1.4% and 5% in the VG and NVG, respectively. Vancomycin can inhibit wound healing. A relative contraindication to instillation of vancomycin is the presence of cerebrospinal fluid leak. The authors recommend further studies to define the optimum doses of intra-wound vancomycin that is required to be instilled to achieve an effective treatment of SSI.

Contributed by Dr. Ashish Aggarwal

Goyal N, et al. Current evidence for anesthesia management during endovascular stroke therapy: Updated systematic review and meta-analysis. J Neurointerv Surg 2018. doi: 10.1136/neurintsurg-2018-013916.

Mechanical thrombectomy (MT) for emergency large vessel occlusion has become a standard form of therapy. The type of anesthesia that should be utilized in performing the procedure remains controversial. The authors have extensively reviewed and analysed all the available literature that involved the use of stent retrievers for MT and compared the clinical outcomes and procedural characteristics among patients undergoing general anesthesia (GA) and local or monitored anesthesia (non-GA). The outcome variables included functional independence (FI; modified Rankin scale [mRS] 0-2), symptomatic hemorrhage, mortality, procedure duration, and vascular and respiratory complications. Sixteen studies (3 randomized control trials [RCTs] and 13 non-RCTs) were identified comprising 5836 patients. When all the studies were analysed, non-GA was associated with higher odds of achieving a 3-month FI and lower odds of achieving a 3-month mortality. However, the sensitivity analyses of only RCTs showed that non-GA was inversely associated with FI while no association was noted with mortality. It was concluded that the updated meta-analysis demonstrated favorable results with non-GA, probably owing to inclusion of non-randomized studies. Recent single-center RCTs indicate that GA is associated with higher odds of FI at 3 months, while other outcomes are similar between the two groups. More trials are, therefore, the need of the hour to define this question better. We believe that until that time, institutional preferences should be followed at individual centres.

Contributed by Dr. Chirag K Ahuja

De Leacy RA, et al. Wide-neck bifurcation aneurysms of the middle cerebral artery and basilar apex treated by endovascular techniques: A multicentre, core lab adjudicated study evaluating safety and durability of occlusion (BRANCH). J Neurointerv Surg 2018. doi: 10.1136/neurintsurg-2018-013771.

A multicentre, retrospective study - BRANCH (wide-neck bifurcation aneurysms of the middle cerebral artery and basilar apex treated by endovascular techniques) was initiated to compare the core laboratory (lab) evaluation of angiographic outcomes with the self-reported outcomes. Consecutive patients were evaluated from 10 US centres with unruptured wide-neck middle cerebral artery (MCA) or basilar apex aneurysms treated endovascularly. Of all the parameters analysed in 115 patients who were enrolled, intervention-related mortality and significant morbidity rates were seen in 1.7% and 5.8% patients, respectively. Core lab adjudicated Raymond Roy outcome ( RR1) and the 2 occlusion rates at follow-up were 30.6% and 32.4%, respectively, while self-reporting had a tendency towards more RR 1 reporting. The retreatment rate within the follow-up window was 8.7% and the incidence of in-stent stenosis at follow-up was 7.9%. The authors concluded that there was a need for novel endovascular devices specifically designed to treat complex intracranial aneurysms. The importance of core lab adjudication in assessing outcomes in such a trial has also been emphasized.

Contributed by Dr. Chirag K Ahuja

Mollan SP, et al. Idiopathic intracranial hypertension: Consensus guidelines on management. J Neurol Neurosurg Psychiatry 2018. doi: 10.1136/jnnp-2017-317440

This was an interesting proposition wherein multi-disciplinary experts from various specialty groups including neurology, neurosurgery, neuroradiology, ophthalmology, nursing and primary care doctors were roped in from across the UK, who had been regularly involved in the management of intracranial hypertension (IH). A specialist interest group was formed to eventually formulate a national consensus guide for optimal management of idiopathic IH. A survey of attitudes and practice in IIH was initially sent to a wide group of physicians and surgeons who investigate and manage IIH regularly. A statement was developed after a comprehensive systematic literature review. Subsequently, an international panel along with four national professional bodies, namely the Association of British Neurologists, British Association for the Study of Headache, the Society of British Neurological Surgeons and the Royal College of Ophthalmologists critically reviewed the statements. A set of over 20 questions were constructed based on the diagnostic principles for the optimal investigation and management of IIH. Final guidelines were formulated based on three main principles: to treat the underlying disease, to protect the vision and to minimize the headache morbidity. This proved to be an excellent attempt at formulating guidelines which could be used for other pathologies too.

Contributed by Dr. Chirag K Ahuja

Rizvi A, et al. Redefining ‘success': A systematic review and meta-analysis comparing outcomes between incomplete and complete revascularization. J Neurointerv Surg 2018. doi: 10.1136/neurintsurg-2018-013950.

Endovascular thrombectomy (EVT) is considered ‘successful' on achieving revascularization of thrombolysis in cerebral infarction (TICI)-2B (complete filling of all of the expected vascular territory but the filling is slower than normal) or greater. Whether or not, this criteria for defining the success of recanalization is adequate or that one should aim at ‘complete' recanalization (TICI -3) in all patients, is a subject of this publication. The authors performed a systematic review and meta-analysis of studies comparing clinical outcomes between patients with TICI-2B and TICI-3 revascularization over the last 5 years. The following outcomes were assessed: a good neurologic outcome (modified Rankin Scale (mRS)≤2 at day 90), mortality, and intracerebral hemorrhage (ICH). In the twenty-one studies (2747 patients) that were identified, patients with TICI-2B revascularization who had mRS ≤2 at day 90 rates were 46%, as compared with 66% for TICI-3 patients. The mortality and ICH rates were also significantly higher in the TICI-2B group than in the TICI-3 group. Thus, it was identified that differences in all major outcome measures were markedly better in patients with complete revascularization when compared with an incomplete but still ‘successful' revascularization using the prior thresholds.

Contributed by Dr. Chirag K. Ahuja

Chen SP, et al. Dynamic changes in white matter hyperintensities in reversible cerebral vasoconstriction syndrome. JAMA Neurol 2018. doi: 10.1001/jamaneurol. 2018.1321.

The establishment of the characteristics and the underlying pathophysiology of white matter hyperintense lesions (WMHs) in patients with reversible cerebral vasoconstriction syndrome (RCVS) was the primary aim of this study. The authors prospectively recruited patients with RCVS over a 3-year period. All patients were subjected to an MRI with three dimensional fluid attenuated inversion recovery (3D FLAIR) sequences as well as transcranial and extracranial color-coded sonography on registration and during the follow-up visits. The WMHs were classified as periventricular or deep and were segmented into 13 anatomical locations. The vascular parameters, including the Lindegaard index (assessing the vasoconstriction severity on sonography), pulsatility index, and resistance index of the internal carotid artery, were independently collected for comparison. The total mean WMH load peaked in the third week after the onset and fell in the fourth week. WMHs were predominantly frontal and periventricular. White matter hyperintensity load correlated strongly with the Lindegaard index during the second week of the disease course and also correlated with the pulsatility index and the resistance index of the internal carotid artery. It was realized that WMHs in patients with RCVS have a dynamic temporal evolution that parallels the disease severity. These WMHs in RCVS may be attributed to the regional hypoperfusion and impaired dampening capacity to the central pulsatile flow.

Contributed by Dr. Chirag K. Ahuja

Jeon SB, et al. Acute brain lesions on magnetic resonance imaging and delayed neurological sequelae in carbon monoxide poisoning. JAMA Neurol 2018;75:436-43.

Currently, no tools exist for assessing the probability of developing delayed neurological sequelae in carbon monoxide (CO) poisoning. The current paper attempts to determine whether or not acute brain lesions visible on diffusion-weighted imaging (DWI) are related to the subsequent development of delayed neurological sequelae after acute CO poisoning. This was a registry-based observational study in 700 patients (aged ≥18 years) with acute CO poisoning. The presence of unambiguous, high-signal-intensity, acute brain lesions on diffusion-weighted imaging (b = 1000 s/mm2) were noted. Delayed neurological sequelae were defined as any neurological symptoms or signs that developed newly within 6 weeks of discharge. Of the 387 patients who fulfilled the inclusion criteria, acute brain lesions on DWI were observed in 26.9% patients - 19.9% had globus pallidus lesions, 3.4% had diffuse lesions, and 14.7% had focal lesions. Delayed neurological sequelae occurred in 26.1% patients. Multivariable logistic regression analysis indicated that the presence of acute brain lesions was independently associated with development of delayed neurological sequelae. The sensitivity and specificity of acute brain lesions to assess the probability of delayed neurological sequelae were 75.2% and 90.2%, respectively. Thus, the presence of acute brain lesions was significantly associated with the development of delayed neurological sequelae.

Contributed by Dr. Chirag K Ahuja

Ramakrishnan TCR, et al. Efficacy and safety of intravenous tenecteplase bolus in acute ischemic stroke: Results of two open-label, multicenter trials. Am J Cardiovasc Drugs 2018. Doi: 10.1007/s40256-018-0284-1.

Tenecteplase (TNK-tPA) is an upcoming and a promising third generation plasminogen activator, because of its greater fibrin specificity and longer half-life than alteplase. Limited studies on intravenous thrombolysis using TNK-tPA are available. This study was done to compare the efficacy and safety of TNK-tPA with alteplase. The first part of the study was an open-label, randomized study in which two doses of TNK-tPA (0.1 and 0.2 mg/kg) were compared and the second part was an open-label study in which TNK-tPA 0.2 mg/kg bolus was compared with historical controls. The primary endpoint for both the studies was an improvement of more than 8 points or a score of 0 on the National Institutes of Health Stroke Scale (NIHSS) [major neurological improvement (MNI)] at 24 h. There was no significant difference in MNI at 24 h between 0.1 and 0.2 mg/kg TNK-tPA doses. The patients given 0.2 mg/kg TNK-tPA had a significantly better 3-month outcome. There were no instances of symptomatic intracerebral hemorrhage (sICH) in the study I. In study II, 62 patients (one lost to follow-up) received 0.2 mg/kg TNK-tPA. MNI was noted in ten patients, a 3-month minimal disability was noted in 37 patients, and a good functional recovery was seen in 33 patients. sICH occurred in one patient, and four patients died. Pooled data of patients in study I and study II receiving 0.2 mg/kg TNK-tPA were compared with data from the historical National Institute of Neurological Disorders and Stroke (NINDS) trial. With TNK-tPA, a greater neurological improvement, minimal disability and a good functional recovery was noted at 3 months. A lower incidence of sICH and a 3-month mortality was noted with TNK-tPA compared with alteplase. Intravenous TNK-tPA 0.2 mg/kg administered within 3 hours of symptom onset seems to be well tolerated and is an effective option in patients with acute ischemic stroke.

Contributed by Dr. Aastha Takkar

Abell JG, et al. Association between systolic blood pressure and dementia in the Whitehall II cohort study: Role of age, duration, and threshold used to define hypertension. Eur Heart J. 2018. doi: 10.1093/eurheartj/ehy288.

This cohort study including 8639 patients was conducted to examine the associations of diastolic and systolic blood pressure (SBP) at age 50, 60, and 70 years with the incidence of dementia, and whether or not the presence of a cardiovascular disease (CVD) in the follow-up period mediates this association.

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the incidence of dementia were ascertained in patients from the Whitehall II cohort study conducted in 1985, 1991, 1997, and 2003. Cubic splines using continuous blood pressure measures suggested that a SBP of greater than or equal to 130 mmHg at age 50 years, but not at age 60 or 70 years was associated with an increased risk of dementia. The findings were confirmed in Cox regression analyses adjusted for sociodemographic factors, health behaviors, and time varying chronic conditions. The diastolic blood pressure was not associated with dementia. Participants with longer exposure to hypertension between the mean ages of 45 and 61 years had an increased risk of dementia compared to those with no or low exposure to hypertension. The authors concluded that a systolic blood pressure of greater than or equal to 130 mmHg at age 50, below the conventional >140 mmHg threshold used to define hypertension, is associated with an increased risk of dementia; in these persons, this excess risk is independent of CVD.

Contributed by Dr. Aastha Takkar

Kamshilin AA, et al. Novel capsaicin-induced parameters of microcirculation in migraine patients revealed by imaging photopletysmography. J Headache Pain 2018;19:43.

Migraine is a common disorder often associated with major morbidity. The non-invasive biomarkers of migraine may help to develop a personalized medication regime for this disorder. Capsaicin-induced skin redness with activated transient receptor potential cation channel subfamily V member 1 (TRPV1) receptors in sensory neurons is associated with the release of the migraine mediator, calcitonin gene-related peptide (CGRP), which has already been widely used in the testing of drugs for migraine. In this study, 14 migraine patients with 14 healthy volunteers were enrolled and a new arrangement of imaging photo plethysmography was used. Blood pulsation amplitude (BPA), observed as an optical-intensity waveform varying synchronously with the heartbeat, was used for the detailed exploration of the microcirculatory perfusion induced by capsicum patch application. Capsaicin-induced high bisphenol A (BPA) areas were distributed unevenly under the patch, forming “hot spots.” Interestingly, the hot spots were much more variable in migraine patients than in the control group. It was concluded that in migraine patients, there is a non-uniform (both in space and in time) reaction to capsaicin, resulting in highly variable openings of the skin capillaries. BPA dynamics measured by imaging photoplethysmography could serve as a novel, sensitive, and non-invasive biomarker of migraine-associated changes in microcirculation.

Contributed by Dr. Aastha Takkar

Hughes R, et al. Oral fingolimod for chronic inflammatory demyelinating polyradiculoneuropathy (FORCIDP Trial): A double-blind multicentre, randomised controlled trial. Lancet Neurol 2018 Jul 6. pii: S1474-4422(18) 30202-3. doi: 10.1016/S1474-4422(18)30202-3.

Fingolimod is now approved for the treatment of relapsing-remitting multiple sclerosis and has been seen to be effective in experimental autoimmune neuritis in animals, a possible model for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This double-blind, multicentre, randomised, placebo-controlled, parallel-group, event-driven study was done at 48 neurology centres. It aimed to evaluate the efficacy of fingolimod in delaying disability progression in patients with CIDP who withdrew from currently effective treatments (intravenous immunoglobulin [IVIg] or corticosteroids). 106 participants with CIDP were randomly assigned (1:1) to once-daily oral fingolimod 0·5 mg or a placebo. The treatment duration was flexible and could be up to 4·5 years. The trial ended in futility after an interim analysis showed that 44 confirmed events with worsening of symptoms had occurred. The adverse events leading to the study discontinuation occurred in seven (13%) participants on fingolimod and none on placebo. Fingolimod 0·5 mg once-daily was considered “not better” than a placebo for the treatment of CIDP. While a relapse after discontinuing intravenous immunoglobulins was considered as a significant factor, further studies are needed to extract any convincing data regarding the use of similar agents in CIDP.

Contributed by Dr. Aastha Takkar

Hanken K, et al. Salivary IL-1β as an objective measure for fatigue in multiple sclerosis? Front Neurol 2018; 9:574.

Fatigue has been an area of huge interest in multiple sclerosis (MS) and other inflammatory disorders. The immunological process itself has been determined as one of the possible causes, triggering neural activity that is experienced as fatigue. The salivary concentration of interleukin (IL)-1β was determined in 116 patients (62 with relapsing remitting MS, 54 with secondary progressive MS) and 51 healthy controls in this study. Fatigue was assessed using various fatigue scales. IL-1β concentration between the groups was compared and it was found out that IL-1β concentration best predicts fatigue scores in relapsing remitting MS patients, even though the IL-1β concentration did not differ significantly between the relapsing remitting MS patients and the healthy controls. Secondary progressive MS patients showed a somewhat elevated IL-1β concentration compared to relapsing remitting MS patients and healthy controls. Furthermore, disease-modifying treatment had a significant effect on the IL-1β concentration, with treated patients showing a lower IL-1β concentration than non-treated patients.

Contributed by Dr. Aastha Takkar

Rathbone E, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. 2018. pii: jnnp-2018-317947. doi: 10.1136/jnnp-2018-317947.

Progression of multiple sclerosis has always remained a key area of research. In order to determine whether or not the ratio of cerebrospinal fluid (CSF) immunoglobulin kappa to lambda free light chains (FLC) at the time of diagnosis of MS predicts disease progression, matched peripheral blood and CSF samples were prospectively collected. The CSF samples were assayed for free and immunoglobulin-associated light chains. The later were also ascertained on B cells and plasmablasts. The clinical follow-up data were collected during a 5-year follow-up period. An increased median CSF κ:λ free light chain was found in all the MS groups but not controls. This ratio predicted expanded disability status scores (EDSS) progression at 5 years, with a lower median EDSS in the group with high CSF κ:λ free light chains. These data demonstrate that CSF immunoglobulin κ:λ ratios, determined at the time of diagnostic lumbar puncture, predict MS disease progression and may, therefore, be useful prognostic markers for an early therapeutic stratification.

Contributed by Dr. Aastha Takkar

Sevim DG, et al. Evaluation of retinal changes in progressive supranuclear palsy and Parkinson disease. J Neuroophthalmol. 2018;38:151-5.

Early in the disease course, differentiating Parkinson disease (PD) from progressive supranuclear palsy (PSP) can be challenging. In this study, the authors used spectral domain optical coherence tomography (SD-OCT) with automatic segmentation to measure the peripapillary nerve fiber layer thickness and the thickness and volume of retinal layers at the macula. The hypothesis was based on the research query on whether or not specific retinal changes could serve as distinguishing features between PD and PSP. The thicknesses of superior peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer, inner plexiform layer, inner nuclear layer, and macular volume were more affected in PSP compared with PD. Thicker inferotemporal pRNFL and lower macular volume were detected in levodopa users compared with nonusers in patients with PD. It was concluded that PD and PSP were associated with distinct changes in retinal morphology, which could be assessed with SD-OCT.

Contributed by Dr. Aastha Takkar

Lamb SE, et al. Dementia and physical activity (DAPA) trial of moderate to high intensity exercise training for people with dementia: Randomised controlled trial. BMJ 2018;361:k1675.

There is insufficient literature of high quality to determine the role of exercise in slowing the cognitive decline in people with dementia. The authors of this study demonstrated that four months of high intensity aerobic and strengthening exercises showed a slight but statistically significant worsening of cognition. There was improvement in physical fitness, but these benefits did not translate into improvement in cognitive impairment or activities of daily living at 1 year. The take home message from this study is that the present evidence shows that moderate-to-high intensity exercise prevents the development of dementia late in life but does not show any effect on improving the slowing of cognitive decline once dementia sets in. Gentle physical activity is good, but effects of high intensity exercise can be rather harmful.

Contributed by Dr. Sahil Mehta

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 International Carotid stenting study is the largest randomised trial which has compared stenting with endarterectomy for symptomatic carotid stenosis. The patients were followed up with serial carotid duplex ultrasound up to 10 years after randomization. The authors in the secondary analysis of the ICSS trial found that moderate restenosis (>50%) was significantly more frequent in the stenting group compared with endarterectomy, but severe (>70%) restenosis rates did not differ between the two procedures. However, patients in the moderate stenosis (>50%) group had higher chances of developing an ipsilateral stroke in the overall population and in the endarterectomy group but not in the stenting group. Further evidence is required to assess the usefulness of a regular follow up of patients after carotid revascularisation with carotid duplex ultrasound. The question on whether a repeat revascularisation procedure is beneficial in those patients with restenosis, also needs to be determined.

Contributed by Dr. Sahil Mehta

Prosperini L, et al. Fingolimod vs dimethyl fumarate in multiple sclerosis: A real- world propensity score- matched study. Neurology 2018;91:e153-e161.

Fingolimod and dimethyl fumarate are the United States Food and Drug Association approved orally recommended treatments for relapsing remitting multiple sclerosis based on randomized controlled trials. This multicentre retrospective post-marketing study from Italy compared the effectiveness of these two drugs on ‘no evidence of disease activity' (NEDA-3). NEDA-3 is defined by absence of relapses, disability worsening and magnetic resonance imaging activity. The authors found no significant difference at a follow up of 18 months between the two drugs on the NEDA-3 status in treatment-naïve patients. However, subgroup analysis suggested the superiority of Fingolimod over dimethyl fumarate in patients who switched from interferons. Further randomized controlled trials with long-term follow-up are needed before these observations can be incorporated into clinical practice.

Contributed by Dr. Sahil Mehta

Wilson D, et al. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischemic stroke or transient ischemic attack (CROMIS-2): A multicentre observational cohort study. Lancet Neurol 2018;17:539-47.

Cerebral microbleeds are round or oval hypointense areas seen on susceptibility weighted magnetic resonance images and pathologically represent hemosiderin laden macrophages. They are potential biomarkers for indicating the presence of cerebral small vessel disease. The authors of this multicentre prospective observational cohort study studied the risk of intracranial haemorrhage following the administration of oral anticoagulants for atrial fibrillation after a recent stroke or TIA. They found that the presence of baseline cerebral microbleeds is independently associated with an increased risk of symptomatic intracranial haemorrhage but not of an increased risk of recurrent ischemic stroke. Further large-scale collaborative observational cohort studies are needed to study the role of microbleeds and incorporate their presence while constituting intracranial haemorrhage risk scores.

Contributed by Dr. Sahil Mehta

Corvol JC, et al. Longitudinal analysis of impulse control disorders in Parkinson disease. Neurology 2018;91:e 189-e201.

Impulse control disorders are common in Parkinson's disease. The use of dopamine agonists represents their main risk factor. The authors of this multicentre longitudinally followed cohort study assessed the dose effect relationship between dopamine replacement therapy and impulse control disorders. PD patients had a duration <5 years and were followed up for upto 5 years. The authors found that the lifetime average daily dose and duration of treatment of dopamine agonists was independently associated with impulse control disorders with a significant dose effect relationship. Similar evidence was not robust for the use of levodopa. Discontinuation of dopamine agonists led to reversal of impulse control disorders. The prevalence of impulse control disorders increased from 20% at baseline to 32% at 5 years with the use of dopamine agonists.

Contributed by Dr. Sahil Mehta

Johnston SC, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med 2018;379:215-25.

The risk of ischemic stroke ranges from 3 to 15% after a minor stroke or transient ischemic attack (TIA). Aspirin reduces the risk of recurrent stroke by 20%. There is evidence from the Chinese population (the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events [CHANCE trial]) that dual antiplatelet therapy initiated within 24 hours after TIA or minor stroke lowers the risk of stroke recurrence by 32%. The authors of this international multicentre randomized trial found that patients with minor ischemic stroke or high-risk TIA (more than or equal to 4 on the ABCD2 score [age >60 years; BP >140/90, clinical features of TIA, duration of symptoms, and a history of diabetes mellitus) who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major and minor haemorrhage than did those receiving aspirin alone. The results of this trial broaden the results of the CHANCE trial to more diverse populations.

Contributed by Dr. Sahil Mehta and Dr. Kuntal Kanti Das

Yu T, et al. High-frequency stimulation of the anterior nucleus of thalamus desynchronizes epileptic network in humans. Brain 2018 doi: 10.1093/brain/awy187.

In search of the treatment of drug-resistant epilepsy, many options have been explored. Deep brain stimulation also holds promise in the treatment. In this interesting paper from China, the investigators have studied the local field potentials in 8 patients having focal drug-resistant epilepsy in the region of the anterior nucleus of the thalamus and have detected very significant observations. They found that high-frequency stimulation in this area leads to desynchronization of epileptic discharges in the areas of the ipsilateral hippocampus. This included interictal epileptic discharges, and this occurred at a frequency of >45 Hz. These findings explain the mechanism of the anterior nucleus of thalamus deep brain stimulation, which probably works through the Papez circuit.

Contributed by Dr. Ravi Yadav

Jankovic J, et al. Safety and tolerability of multiple ascending doses of PRX002/RG7935, an anti-α-synuclein monoclonal antibody, in patients with Parkinson disease: A randomized clinical trial. JAMA Neurol 2018 doi: 10.1001/jamaneurol. 2018.1487.

Targeting therapies against pathological proteins have a potential to cure proteinopathies like Parkinson's disease that have an abnormal alpha synuclein deposition in multiple areas of the body and brain. In this paper, Jankovic et al., publish the results of a humanized anti-alpha synuclein monoclonal antibody in patients with Parkinson's disease. They studied this by giving escalating doses of the study drug directed against aggregated alpha synuclein with a view to reduce the spread of the disease. The patients received intravenous infusions every 4 weeks over a period of 24 weeks. Overall, the drug was well tolerated, and the side effects were tolerable. The drug levels in cerebrospinal fluid also reached a satisfactory extent that would help in binding the aggregated alpha-synuclein.

Contributed by Dr. Ravi Yadav

Montaut S, et al., French Parkinson's and Movement Disorders Consortium. Assessment of a targeted gene panel for identification of genes associated with movement disorders. JAMA Neurol 2018 doi: 10.1001/jamaneurol.2018.1478.

The assessment of movement disorders and reaching to a definitive pathogenetic mechanism is difficult due to the significant phenotypic and genetic heterogeneity. This paper attempts to propose a genetic testing algorithm that would help to assess the movement disorders in a better and a more systematic way. 378 patients of  Parkinsonism More Details, dystonia, myoclonus, paroxysmal movement disorders and ataxias were assessed by whole exome sequencing that included a 127 gene panel. The results showed that the pickup rate of the genes that were associated with parkinsonism was about 55%, and was 25% for dystonia. For the other diseases, it was about 8%. The authors concluded that the high coverage sequencing panel could be cost effective in the evaluation of patients with movement disorders.

Contributed by Dr. Ravi Yadav

Hyacinth HI, et al. Association of sickle cell trait with ischemic stroke among African Americans: A meta-analysis. JAMA Neuol 2018 doi: 10.1001/jamaneurol. 2018.0571.

It has been long known that African Americans are more predisposed to stroke; however, it is unclear whether sickle cell trait was a cause of high risk of stroke among them. In this meta-analysis, Hyacinth et al., included the data from 19,464 African Americans from 4 large studies. After adjustment of other risk factors, the hazard ratio of ischemic stroke independently associated with sickle cell trait in the meta-analysis was 0.80 (95% confidence interval, 0.47-1.35; P = 0.82). The individual cohorts have also shown similar results. The results show that sickle cell trait is not a risk factor for ischemic stroke. Alternate causes should be investigated in these group of patients.

Contributed by Dr. Ravi Yadav

Patodia S, et al. The ventrolateral medulla and medullary raphe in sudden unexpected death in epilepsy. Brain 2018;141:1719-33.

Sudden unexpected death in epilepsy (SUDEP) has been one of the leading causes of premature death in patients with epilepsy. One of the hypothesis to explain this event is the post-ictal respiratory depression and the abnormality in neuromodulation of medullary nuclei related to respiration. The authors investigated the neurons in the ventrolateral medulla and the medullary raphe. The authors studied the brainstem of forty patients comprising of four groups. There were 14 cases with SUDEP, six epilepsy controls, seven Dravet syndrome cases and 13 non-epilepsy controls. After extensive evaluation of the medulla using various immunohistochemical techniques and automated analysis, the authors found that there was a significant reduction of neuropeptidergic, monoaminergic, galaninergic and serotoninergic systems, thus showing the reduction of their neuromodulatory role. They also suggested an evaluation of the other nuclei to look for other changes. These findings were thought of as being due to previous seizures and could serve as a risk factor of SUDEP.

Contributed by Dr. Ravi Yadav and Dr. Sahil Mehta

Mestre TA, et al. Rating scales and performance-based measures for assessment of functional ability in Huntington's disease: Critique and recommendations. Mov Disord Clin Pract 2018 doi: 10.1002/mdc3.12617.

Various scales have been used in the studies performed on patients with Huntington's disease (HD). However, the clinometric properties of the scales have not been studied systematically and thus there is no uniformity. The International Parkinson's and Movement disorders society (MDS) formed a group to look on this aspect and come out with the recommendations. They evaluated 29 scales and grouped them into either (a) performance based measures; or (b) rating scales. There were three performance based measures that were labelled as recommended: the Tinneti mobility test for screening of risk of falls, the Berg balance scale and the six minute walk test. They did not recommend any rating scale. They finally concluded that there is a need to develop meaningful scales that capture small but meaningful changes in various parameter in patients with HD.

Contributed by Dr. Ravi Yadav

Winkelmann J, et al. Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017). Mov Disord 2018. doi: 10.1002/mds.27260.

This evidence based review was done after 10 years of the previously published review on the same topic. This review incorporates the last 10 years' papers from January 2008 to January 2017 published on the same topic. Forty new studies were reviewed in this paper. Pregabalin, gabapentin and oxycodone related studies were reviewed for the first time. The drugs that were considered efficacious, which are findings similar to that seen in the data of 2018, were levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. The drugs considered likely efficacious were bromocriptine, oxycodone, carbamazepine, and valproic acid. Augmentation of the symptoms of restless legs syndrome was the most important long-term treatment complication associated with pramipexole and all other DOPA agonists. This effect was much more than was seen with pregabalin. The committee also recommended safety monitoring for the drugs like cabergoline, pergolide, oxycodone, methadone, tramadol, carbamazepine, and valproic acid.

Contributed by Dr. Ravi Yadav

Hseish MK, et al. The influence of spinopelvic parameters on adjacent-segment degeneration after short spinal fusion for degenerative spondylolisthesis. J Neurosurg: Spine DOI: 10.3171/2018.2.SPINE171160.

The authors retrospectively analysed 30 patients (9 males and 21 females; mean age – 64 years), operated for short lumbar and lumbosacral fusion surgeries between August 2003 and July 2010, who developed adjacent segment disease (ASD). Thirty matched patients (21 women and 9 men with their mean age being 63 years) without ASD comprised the control group, according to the following matching criteria: same diagnosis on admission, similar pathologic level (≤1 level difference), similar gender, and age. The average follow-up was 6.8 years (range 5–8 years). The spinopelvic parameters had no significant influence on ASD after a short segment spinal fusion. The authors concluded that neither the spinopelvic parameters nor a mismatch of pelvic incidence and lumbar lordosis were significant factors responsible for ASD after a short segment spinal fusion due to a single-level degenerative spondylolisthesis.

Contributed by Dr. Anant Mehrotra

Fujii Y, et al. Threshold of the extent of resection for WHO grade III gliomas: Retrospective volumetric analysis of 122 cases using intraoperative MRI. J Neurosurg DOI: 10.3171/2017.3.JNS162383.

Clinical and radiological data from 122 patients with newly diagnosed World Health Organisation (WHO) grade III gliomas who had undergone intraoperative magnetic resonance imaging (MRI)–guided resection at a single institution between March 2000 and December 2011 were analysed retrospectively. The patients were divided into 2 groups based upon their histological subtypes: 81 patients had an anaplastic astrocytoma (AA) or an anaplastic oligo-astrocytoma (AOA), and 41 patients had an anaplastic oligodendroglioma (AO). The extent of resection (EOR) was calculated using pre- and postoperative T2-weighted and contrast-enhanced T1-weighted MR images. The 5-, 8-, and 10-year overall survival (OS) rates for all patients were 74.28%, 70.59%, and 65.88%, respectively, in the three groups. The 5- and 8-year OS rates for patients with AA and AOA were 72.2% and 67.2%, respectively, and the 10-year OS rate was 62.0%. On the other hand, the 5- and 8-year OS rates for patients with AO were 79.0% and 79.0%; the 10-year OS rate is not yet available. The median pre- and postoperative T2-weighted high–signal intensity volumes were 56.1 cm3 (range 1.3–268 cm3) and 5.9 cm3 (range 0–180 cm3), respectively. The median EOR of T2-weighted high–signal intensity lesions (T2-EOR) and contrast-enhanced T1-weighted lesions were 88.8% (range 0.3%–100%) and 100% (range 34.0%–100%), respectively. A significant survival advantage was associated with resection of 53% or more of the preoperative T2-weighted high–signal intensity volume in patients with AA and AOA, but not in patients with AO. The univariate analysis showed that the preoperative Karnofsky performance scale score (P = 0.0019), isocitrate dehydrogenase 1 (IDH1) mutation (P = 0.0008), and T2-EOR (P = 0.0208) were significant prognostic factors that influenced survival in patients with AA and AOA. The multivariate analysis demonstrated that T2-EOR (hazard ratio [HR] 3.28; 95% confidence interval [CI] 1.22–8.81; P = 0.0192) and isocitrate dehydrogenase (IDH) 1 mutation (HR 3.90; 95% CI 1.53–10.75; P = 0.0044) were predictive of survival in patients with AA and AOA.

Contributed by Dr. Anant Mehrotra

Mallinova V, et al. The impact of temporary clipping during aneurysm surgery on the incidence of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2018;129:84-90.

The authors retrospectively analysed 778 patients who underwent clipping for an aneurysm after subarachnoid haemorrhage. Apart from the surgical parameters, the authors recorded the transcranial Doppler (TCD) sonography–documented vasospasm (TCD-vasospasm, blood flow acceleration >120 cm/sec) findings, as well as the development of delayed ischemic neurological deficits (DINDs), and delayed cerebral infarction (DCI). Temporary clipping was performed in 338 (43.4%) of 778 patients during the aneurysm surgery. TCD sonographic flow acceleration developed in 370 (47.6%), DINDs in 123 (15.8%), and DCI in 97 (12.5%) patients. Patients with temporary clipping showed no significant increase in the incidence of TCD-vasospasm compared with patients without temporary clipping (49% vs 48%, respectively; P = 0.60). DINDs developed in 12% of patients with temporary clipping and in 18% of those without temporary clipping (P = 0.01). DCI occurred in 9% of patients with temporary clipping and in 15% of those without temporary clipping (P = 0.02). The need for rescue temporary clipping was a predictor for DCI; 19.5% of patients in the rescue temporary clipping group and only 11.3% in the elective temporary clipping group had infarcts (P = 0.02). Elective temporary clipping was not associated with an increased incidence of TCD-vasospasm (P = 0.31), DIND (P = 0.18), or DCI (P = 0.06).

Contributed by Dr. Anant Mehrotra

Riva M, et al. Indocyanine green video angiography in aneurysm surgery: Systematic review and meta-analysis. Neurosurgery 2018;83:166-80.

The authors conducted a systematic literature review and found 2871 records (in Pubmed search) from January 2003 to April 2016; of these, 20 articles were eligible for microscopic visual observation (primary endpoint 1) and 11 for DSA (digital subtraction angiogram, primary endpoint 2). The rate of mis-clipping that eluded microscopic visual observation and was identified at indocyanine green video angiography (ICG-VA) was 6.1% (95% confidence interval (CI): 4.2-8.2), and the rate of mis-clipping that eluded ICG-VA and was identified at DSA was 4.5% (95% CI: 1.8-8.3). The authors concluded that because a proportion of mis-clippings cannot be identified with ICG-VA, this technique should still be considered complementary rather than a replacement to DSA during aneurysm surgery. Incorporation of other intraoperative tools, such as flowmetry or electrophysiological monitoring, can obviate the need for an intraoperative DSA for the identification of vessel stenosis. Nevertheless, DSA likely remains the best tool for the detection of aneurysm remnants.

Contributed by Dr. Anant Mehrotra

Gogineni E, et al. Long-term survivorship following stereotactic radiosurgery alone for brain metastases: Risk of intracranial failure and implications for surveillance and counseling. Neurosurgery 2018;83:203-9.

The authors identified 132 patients with brain metastases treated initially with stereotactic radiosurgery (SRS) alone (± pre-SRS surgical resection) with at least 2 years of survival and follow-up after receiving the SRS treatment. The primary study endpoints were the rates of actuarial intracranial progression beyond 2 years, calculated using the Kaplan–Meier and Cox regression methods. The median follow-up from the first course of SRS was 3.5 years. The significant predictors of an intracranial failure beyond 2 years included the presence of intracranial failure before 2 years (52% vs 25%, P < 0.01) and the total SRS tumor volume ≥5 cc (51% vs 25%, P < 0.01). On parsimonious multivariate analysis, failure of treatment before 2 years (hazard ratio (HR) = 2.2, 95% confidence interval (CI): 1.2-4.3, P = 0.01) and total SRS tumor volume ≥5 cc (HR = 2.3, 95% CI: 1.2-4.3, P = 0.01) remained significant predictors of an intracranial relapse beyond 2 years.

Contributed by Dr. Anant Mehrotra

Walker WC, et al. Predicting long-term global outcome after traumatic brain injury: Development of a practical prognostic tool using the traumatic brain injury model systems national database. J Neurotrauma 2018;35:1587-95.

This study aimed to propose an easy-to-use clinical tool to council family members regarding the prognostication of the survivors of moderate-to-severe traumatic brain injuries (TBI). Prospectively collected data from the TBI-Model Systems (TBIMS) inception cohort study formed the basis of the statistical computations used in this article. Patients with non-penetrating TBI studied between 1997 and 2017 in 17 predesignated rehabilitation facilities were analyzed. The sample sizes were 10,125 (year-1), 8,821 (year-2), and 6,165 (year-5) after cross-sectional exclusions (death, vegetative state, insufficient post-injury time, and unavailable outcome). Post-traumatic amnesia (PTA), age, pre-morbid education, productivity, and occupational category before the trauma were found to be important variables of the eventual outcome. PTA was the only significant factor contributing to the predictability of Glasgow outcome score (GOS). Generally, patient outcomes improved with a shorter duration of PTA, a younger age, a greater pre-morbid productivity, and a higher pre-morbid vocational or educational achievement. Across all the prognostic groups, the best and the worst good recovery rates were 65.7% and 10.9%, respectively, and the best and worst severe disability rates were 3.9% and 64.1%, respectively. The length of PTA, a clinical marker of injury severity, was by far the most critical outcome determinant.

Contributed by Dr. Kuntal K. Das

Coughlan M, et al. A prospective, randomized, multicenter study comparing silicated calcium phosphate versus BMP-2 synthetic bone graft in posterolateral instrumented lumbar fusion for degenerative spinal disorders. Spine (Phila Pa 1976). 2018;43:E860-E868.

Degenerative lumbar spondylosis is a common disorder. In this condition, many of the patients undergo fusion of the affected levels for achieving a sustained postoperative favorable outcome. Promoting fusion usually requires the placement of autologous bone grafts with or without bone morphogenic protein-2 (BMP-2). This study aimed to assess the utility of silicated calcium phosphate (SiCaP) in providing stable postoperative fusion in comparison with BMP-2 after a combined posterior lumbar interbody fusion (PLIF) and posterolateral fusion (PLF), without the use of any other osteoconductive/osteoinductive graft materials. The authors assessed their patients radiographically within 2 years of surgery. Clinical outcomes (pain on visual analog scale, Oswestry Disability Index, SF-36) and adverse events (AEs) were monitored. At 12 months, fusion was achieved in 25 of 35 (71.4%) of the SiCaP group, and 20 of 27 (74.1%) patients of the BMP-2 group, respectively (P=1.000). At 24 months, the fusion rate was 78.6% and 84.8% for the SiCaP and BMP-2 groups, respectively (P=0.5613). The improvement in clinical outcomes was similar in both the groups over time, without there being any differentiable adverse events in any specific group, indicating that SiCaP could become an effective alternative to BMP-2 for spinal surgeons performing these procedures.

Contributed by Dr. Kuntal K. Das

Chin AL, et al. Survival impact of postoperative radiotherapy timing in pediatric and adolescent medulloblastoma. Neuro Oncol 2018;20:1133-41.

Medulloblastoma is a highly malignant tumor and mandates adjuvant chemo-radiation to maximize survival after a resective surgery. It is always a concern for any neurosurgeon that the advantage gained by maximal tumor excision could be offset by a delay in the initiation of adjuvant therapy. This article precisely tries to answer the issue of the ideal timing of adjuvant therapy. Among the 1338 pediatric and adolescent patients analyzed, early radiotherapy [RT] (defined as initiation of RT ≤3 weeks after surgery) was seen to be offered to younger patients, in those in M1-3 disease, and in those with a subtotal resection. Contrary to our usual belief and to our great surprise, patients who initiated RT early had decreased 5-year over-all survival compared with patients who initiated RT thereafter (P = 0.009). The highest survival (80.5%) was obtained in patients who started their RT between 3-4 weeks of surgery. Interestingly, those in whom RT started after 5 weeks of surgery but within 3 months of surgery survived more than those in the early RT group (79.4% Vs 72.5%). The results persisted even after a multivariate analysis, indicating that the timing of RT was an independent predictor of survival, albeit in contradiction to our conventional belief.

Contributed by Dr. Kuntal K. Das

Vanderbeek AM, et al. The clinical trials landscape for glioblastoma: Is it adequate to develop new treatments? Neuro Oncol 2018;20:1034-43.

In this interesting review article, the authors intended to explore the reasons behind the lack of significant advances in the treatment of glioblastoma (GBM) despite a mammoth increase in the the scientific understanding of the disease. The authors focussed particularly on the current clinical trial landscape that evaluated newer therapies and biomarkers. Various clinical trials conducted between 2005 and 2016 were scrutinized to answer this question. They found that only a very small proportion of the patients actually enrolled for these trials. In addition, almost all of these trials took nearly 3-4 years to complete. The number of trials in phase III were only 26% compared to a figure of 93% in phase I and II. To make matters worse, only 1 of the 8 completed phase III trials reported positive results. The lack of randomization of many of the phase II trials also contributed to the lack of substantial data emanating from the phase III trials.

Contributed by Dr. Kuntal K. Das






 

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Online since 20th March '04
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