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Table of Contents    
NI FEATURE: THE FOURTH DIMENSION - COMMENTARY
Year : 2019  |  Volume : 67  |  Issue : 3  |  Page : 837-855

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


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

Date of Web Publication23-Jul-2019

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: 10.4103/0028-3886.263220

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How to cite this article:
Turel MK, Tripathi M, Aggarwal A, Singla N, Ahuja CK, Takkar A, Mehta S, Garg K, Yadav R, Mehrotra A, Das KK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India 2019;67:837-55

How to cite this URL:
Turel MK, Tripathi M, Aggarwal A, Singla N, Ahuja CK, Takkar A, Mehta S, Garg K, Yadav R, Mehrotra A, Das KK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India [serial online] 2019 [cited 2019 Aug 23];67:837-55. Available from: http://www.neurologyindia.com/text.asp?2019/67/3/837/263220




Li S, et al. Mannitol improves intraoperative brain relaxation in patients with a midline shift undergoing supratentorial tumor surgery: A randomized controlled trial. J Neurosurg Anesthesiol 2019 doi: 10.1097/ANA.0000000000000585.

In this randomized, controlled double-blinded study, 204 patients with preoperative midline shift undergoing elective supratentorial brain tumor surgery were equally allocated to receive placebo or 0.7, 1.0, or 1.4 gm/kg mannitol infusion. The primary outcome was the proportion of satisfactory brain relaxation. Demographics and baseline characteristics were similar among the 4 groups. Trend analysis showed that mannitol infusion increased satisfactory brain relaxation, relaxed dural tension as well as provided an adequate surgical exposure, and decreased the requirement for rescue therapy for brain swelling, all in a dose-dependent manner. The tumor size, peritumoral edema and the dose of mannitol infused were significantly associated with satisfactory brain relaxation. An increased risk of moderate to severe postoperative cerebral edema was found in the group receiving 1.4 g/kg mannitol in a dose-dependent manner. The authors concluded that an optimal mannitol infusion dosage of 1 gm/kg is recommended to improve brain relaxation with a lower risk of moderate to severe postoperative cerebral edema in patients with midline shift undergoing supratentorial tumor resections. They also concluded that the effect of mannitol on brain relaxation was affected by the size of the tumor and the severity of peritumoral edema, rather than by midline shift.

Contributed by Dr. Mazda K. Turel

Rajakulendran N, et al. WNT and Notch signalling govern self-renewal and differentiation in a subset of human glioblastoma stem cells. Genes Dev 2019 doi: 10.1101/gad.321968.118.

Developmental signal transduction pathways tend to act diversely, with context-dependent roles across different systems and disease types. Glioblastomas (GBMs), strongly resemble developmental systems, but these growth processes have not yet been exploited therapeutically. It is likely in part due to the extreme cellular and genetic heterogeneity in these tumors. The role of WNT/β catenin signalling in GBM stem cell (GSC) renewal and fate decisions remain controversial. Here, the authors report context-specific actions of WNT/β catenin signalling in directing cellular fate specification and renewal. A subset of primary GBM-derived stem cells requires WNT proteins for self-renewal, and this subset specifically relies on WNT/β catenin signalling for an enhanced tumor burden in xenograft models. In an orthotopic WNT reporter model, WNT hi GBM cells (which exhibit high levels of β catenin signalling) are a faster-cycling, highly self-renewing stem cell pool. In contrast, WNT lo cells (with low levels of signalling) are slower cycling and have decreased self-renewing potential. Dual inhibition of WNT/β catenin and Notch signalling in GSCs that express high levels of the proneural transcription factor ASCL1 leads to robust neuronal differentiation and inhibits clonogenic potential. This work identifies new contexts for WNT modulation for targeting stem cell differentiation and self-renewal in GBM heterogeneity, which deserve further exploration therapeutically.

Contributed by Dr. Mazda K. Turel

Cloughesy TF, et al. Neoadjuvant anti-PD 1 immunotherapy promotes a survival benefit with intratumoral and systemic immune response in recurrent glioblastoma. Nat Med 2019;25:477-86.

The authors conducted a randomized, multi-institution clinical trial to evaluate the immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to the patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with an upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients who received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment enhanced the clonal expansion of T cells, decreased the PD-1 expression on peripheral blood T cells and led to a decreased monocytic population more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade could enhance both local and systemic antitumor immune responses and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor.

Contributed by Dr. Mazda K. Turel

Srivatsan A, et al. Middle meningeal artery embolization for chronic subdural hematoma: Meta-analysis and systematic review. World Neurosurg 2019;122:613-9.

Chronic subdural hematoma is a very common neurosurgical condition. Although conventional surgical methods, such as burr hole irrigation, have been the mainstay of treatment, middle meningeal artery (MMA) embolization has emerged as a promising adjunct or alternative treatment. The aim of this article was to present a meta-analysis and systematic review of this topic. Three double-arm studies comparing embolization and conventional surgery groups and 6 single-arm case series were identified and analyzed. Hematoma recurrence rate was significantly lower in the embolization group compared with the conventional treatment group (2.1% vs. 27.7%); surgical complication rates were similar between the groups (2.1% vs. 4.4%). The number of patients with modified Rankin Scale score >2 in the embolization (12.5%) versus the conventional treatment (9.1%) group showed no statistical difference. The authors thus concluded that MMA embolization was a promising treatment for chronic subdural hematoma.

Contributed by Dr. Mazda K. Turel

Martin E, et al. Randomized controlled trials comparing surgery to non-operative management in neurosurgery: A systematic review. Acta Neurochir (Wien) 2019;161:627-34.

A randomized controlled trial (RCT) remains the pinnacle of clinical research design. This study set out to assess the trial design, their quality and identify their influence on the outcomes in recent neurosurgical trials comparing surgery to non-operative treatment. Eighty-two neurosurgical RCTs were identified, 40 in spine disorders, 19 in neurovascular and neurotrauma, 11 in functional neurosurgery, ten in peripheral nerve surgery, and two in pituitary surgery. Eighty-four RCTs were registered, of which some were still ongoing. Trial registration rate differed per subspecialty. Funding was mostly from non-industry institutions (59%), but 26% of RCTs did not report their funding sources. 36% of RCTs did not report a difference between the surgical and the non-operative treatment, 3.7% favored a non-operative management. Primary and secondary outcome measures were changed in 13% and 34% of RCTs respectively and varied by subspecialty. 42% of RCTs subtracted ≥10% of the anticipated accrual and 13% of RCTs added ≥10%. 7.3% of registered RCTs were terminated, mostly due to a rather slow recruitment. Subspecialty, registration, funding, masking, population size, and changing outcome measures were not significantly associated with a reported benefit of surgery. Neurosurgical RCTs comparing surgical to non-operative treatment often find a benefit for surgical treatment. This study showed that the changes to outcome measurements and anticipated accrual are common and funding sources are not always reported.

Contributed by Dr. Mazda K. Turel

Savardekar AR, et al. Timing of carotid endarterectomy for symptomatic carotid stenosis: A snapshot of current trends and systematic review of literature on changing paradigm towards early surgery. Neurosurgery 2019 doi: 10.1093/neuros/nyy557.

Carotid revascularization has been recommended as the maximally beneficial treatment for stroke prevention in patients with recently symptomatic carotid stenosis (SCS). The appropriate timing for performing carotid endarterectomy (CEA) within the first 14 days after the occurrence of the index event remains controversial. A systematic review of literature was conducted to study the timing of CEA for SCS. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) were followed. A total of 63 articles were identified as relevant to this topic. A summary of 15 articles favoring urgent CEA (within 48 h) for SCS within 48 h of the index event, and 9 articles not favoring an urgent CEA were presented. Thus, a consensus was still to be achieved on the ideal timing of CEA for SCS within the 14-day window presently prescribed. The current literature suggests that patients who undergo urgent CEA (within 48 h) after nondisabling stroke as the index event had an increased periprocedural risk as compared to those who had transient ischemic attack (TIA) as the index event. Further prospective studies and clinical trials studying this question with separate groups classified as per the index event are required to shed more light on the subject. The current literature points to a changing paradigm towards early carotid surgery, specifically targeted within 48 h if the index event is TIA, and within 7 d if the index event is a stroke.

Contributed by Dr. Mazda K. Turel

Mallet L, et al. Long-term effects of subthalamic stimulation in obsessive-compulsive disorder: Follow-up of a randomized controlled trial. Brain Stimul 2019 doi: 10.1016/j.brs. 2019.04.004.

Obsessive-compulsive disorder (OCD) is characterized by intrusive, anxious thoughts with repetitive, ritualized behaviors, and has a negative impact on family relationships and the social life. The authors prospectively followed 14 OCD patients treated with subthalamic deep brain stimulation [DBS] (STN-DBS, STOC study) for 46 months. The primary outcome was the change in the total Yale Brown Obsessive Compulsive Scale (Y- BOCS) score between inclusion (baseline) and month 46, which showed a median change of 50%. At the final follow-up, 92% were considered at least partial responders and 75% as full responders. During the follow-up, the medication had not changed significantly but stimulation voltage had to be significantly increased. These results show that STN-DBS could effectively treat OCD symptoms in severe and refractory patients over a period more than 3 years.

Contributed by Dr. Mazda K. Turel

Fu C, et al. Surgical management of moderate basal ganglia intracerebral hemorrhage: Comparison of safety and efficacy of endoscopic surgery, minimally invasive puncture and drainage, and craniotomy. World Neurosurg 2019 doi: 10.1016/j.wneu. 2018.10.192.

To date, no standard surgical procedure has been proven effective for intracerebral hemorrhage (ICH), particularly the deep hematomas. The patients with basal ganglia ICH (N = 177) were divided into 3 groups based on the intervention that they underwent: Endoscopic surgery group (n = 61), minimally invasive puncture and drainage group (n = 60), and craniotomy group (n = 56). Minimally invasive puncture and drainage was the least traumatic procedure and had the shortest operative times, but it could not remove the hematoma quickly; moreover, it had the highest rebleeding rate. Craniotomy was effective in removing the hematoma but resulted in marked trauma and had the highest incidence of pulmonary infection. Endoscopic surgery was safer and more effective than the other 2 surgical methods, with greater improvements in neurologic outcomes and no change in mortality.

Minimally invasive neuroendoscopic management had the advantages of direct vision, efficient hematoma evacuation, and relatively good results. Therefore, endoscopic surgery may be a more promising approach for the treatment of moderate sized basal ganglia ICH.

Contributed by Dr. Mazda K. Turel

Nene AM, et al. Six versus 12 months of anti tubercular therapy in patients with biopsy proven spinal tuberculosis: A single center, open labelled, prospective randomized clinical trial-A pilot study. Spine (Phila Pa 1976) 2019;44:E1-E6.

A prospective randomized open labelled clinical trial of 6 versus 12 months anti-tubercular therapy (ATT) in patients with biopsy proven spinal-vertebral tuberculosis was undertaken. The primary end point was the absence of disease recurrence 24 months after completing the therapy. The secondary end points were: clinical cure at the end of the therapy, development of significant adverse effects of ATT, need for delayed surgery, and residual neurological dysfunction. A hundred patients, randomized to 6 or 12 months of ATT, were followed up for a minimum of 24 months after completion of the therapy. All patients completed the scheduled duration of ATT, with only one crossover from the 6 months ATT group to the 12 months group. There were no disease recurrences at a 24-month follow up period. All 100 patients met the criteria for cure at the time of stopping medicines. One patient (12 months group) had residual neurological dysfunction at the time of treatment completion, which completely resolved over the next 12 months. There were no patients with major drug induced hepatitis. None needed surgical re-exploration for persistent infection or implant removal. This pilot study concludes that, in patients with biopsy proven spinal-vertebral TB, 6 and 12 months of ATT give similar clinical outcomes at 24 months of completion of therapy. This requires validation in our country; and also, whether or not the same holds true for multi-drug resistant TB infection, needs further studies.

Contributed by Dr. Mazda K. Turel

Dunn LK, et al. The impact of alvimopan on return of bowel function after major spine surgery - A prospective, randomized, double-blind study. Neurosurgery 2019 doi: 10.1093/neuros/nyz005.

The authors aimed to investigate the impact of alvimopan, a peripheral mu-receptor antagonist in opioid-naive patients undergoing major spine surgery. The patients undergoing >3 levels of thoracic and/or lumbar spine surgery were enrolled in this prospective, randomized, double-blinded study to receive either alvimopan or a placebo prior to and following the surgery. A total of 24 patients were assigned to the active group and 25 to the placebo group. Postoperatively, the alvimopan group reported significantly earlier resumption of first solid intake, passing of flatus, and the first bowel movement. The alvimopan group had higher pain scores; however, there was no significant difference between the groups with respect to the postoperative opioid use. This study shows that the perioperative use of alvimopan significantly reduced the time to return of bowel function with no increase in postoperative opioid use, albeit with less optimal pain control.

Contributed by Dr. Mazda K. Turel

Peolsson A, et al. Postoperative structured rehabilitation in patients undergoing surgery for cervical radiculopathy: A 2-year follow-up of a randomized controlled trial. J Neurosurg Spine 2019 doi: 10.3171/2018.12.SPINE181258.

Information about the postoperative rehabilitation for cervical radiculopathy (CR) is scarce. The aim of this study was to investigate the additional benefits of a structured postoperative rehabilitation (SPT), compared with a pragmatic standard postoperative approach (SA), in which rehabilitation was used as needed and patients sought physiotherapy on their own without a referral. The study subjects were the patients with MRI evidence of disc herniation and concomitant clinical signs who underwent surgery for CR. The patients (n = 202) were randomized to receive SPT or SA. The main outcome was the Neck Disability Index (NDI) score. SPT provided no additional benefits over SA at the postoperative 2-year follow-up. Both groups improved over time, with no reported adverse effects. The authors conclude that SPT offered no additional benefits over SA; however, patients tolerated postoperative neck exercises without any negative side effects. These findings are important for the development of future active and neck-specific postoperative rehabilitation interventions for patients with CR.

Contributed by Dr. Mazda K. Turel

Petr O, et al. Immediate versus delayed surgical treatment of lumbar disc herniation acute motor deficits: The impact of surgical timing on functional outcome. Spine (Phila Pa 1976) 2019;44:454-63.

The aim of the study was to assess the impact of time-to-surgery in patients with motor deficits (MDs) in lumbar disc herniation (LDH). A total of 330 patients were included and were classified into two categories: Group I included all patients with paresis <48 hours and Group II included all patients with paresis >48 hours. The group I showed a significantly faster recovery of moderate/severe paresis (Medical Research Council 0-3) at discharge, and at a 3-month follow up (P ≤ 0.001), whereas there were no significant differences in recovery of mild paresis (Medical Research Council 4). Sensory deficits also recovered substantially faster in Group I at a 6-week (P = 0.003) and 3-month follow up (P = 0.045). The body mass index, preoperative Medical Research Council (MRC) grade, and duration of MDs were identified as significant predictors for recovery of paresis at all follow visits with a substantial impact on the patient reported outcomes including sciatica and/or dermatomal sensory deficits. Given the superior rates of neurological recovery of acute moderate/severe MDs, immediate surgery should be the primary option according to the authors.

Contributed by Dr. Mazda K. Turel

Bae IS, et al. Medial branch block versus vertebroplasty for 1-level osteoporotic vertebral compression fracture: 2-Year retrospective study. World Neurosurg 2019;122:e1599-e1605.

The authors compared the use of percutaneous vertebroplasty (VP) and medial branch block (MBB) to treat osteoporotic vertebral compression fractures (VCF) in 164 patients. The clinical outcomes were measured with a visual analogue scale (VAS) and the Oswestry disability index (ODI). The patients were divided into 2 groups: 72 patients in the conservative group treated by MBB (the MBB group) and 92 patients in the group who underwent VP (the VP group). The VAS and ODI scores improved significantly within the first postoperative week in the VP group compared to the MBB group. However, the VAS and ODI scores did not differ after the first postoperative year. After 2 years of follow-up, 14 new fractures occurred in the VP group and 3 in the MBB group. The improvement in compression ratio was statistically greater in the VP group than in the MBB group. However, after 2 years, the radiologic changes between the groups did not differ statistically. After the final follow-up visits, the hospital costs were significantly lower in the MBB group. The authors thus concluded that VP and MBB both had similar efficacy in terms of pain relief and radiologic changes at follow-up, with MBB being more cost effective than VP.

Contributed by Dr. Mazda K. Turel

Yerneni K, et al. Topical tranexamic acid in spinal surgery: A systematic review and meta-analysis. J Clin Neurosci 2019;61:114-9.

Tranexamic acid (TXA) is a commonly used antifibrinolytic agent for perioperative blood conservation in several surgical specialties. Although historically administered intravenously, such systemic administration may be accompanied by severe side effects. Thus, the topical usage of TXA has been established in several fields but remains poorly evaluated in spine surgery. In this study, the authors aimed to review the medical literature on topical TXA usage in spine surgery to evaluate its safety and efficacy. They identified five articles and one unpublished clinical trial that were placebo-controlled and comprised 218 patients. The patients receiving topical TXA demonstrated a significantly lower postoperative blood loss as compared to the placebo group and had a shorter hospital stay. Overall, topical TXA favorably reduced the postoperative blood loss and hospitalization duration in patients undergoing spinal surgery. However, further randomized controlled trials will be needed to definitively establish the optimal therapeutic doses needed for hemorrhage management, and the pharmacodynamics of tTXA in spinal surgery.

Contributed by Dr. Mazda K. Turel

Chan AK, et al. A comparison of minimally invasive transforaminal lumbar interbody fusion and decompression alone for degenerative lumbar spondylolisthesis. Neurosurg Focus 2019;46:E13.

The optimal minimally invasive surgery (MIS) approach for grade 1 lumbar spondylolisthesis is not clearly elucidated. In this study, the authors compared the 24-month patient-reported outcomes (PROs) after MIS transforaminal lumbar interbody fusion (TLIF) and MIS decompression for degenerative lumbar spondylolisthesis. A total of 143 patients underwent MIS (72 MIS TLIF [50.3%] and 71 MIS decompression [49.7%]). PROs included the Oswestry disability index (ODI), numeric rating scale (NRS) for back pain, NRS for leg pain, EuroQol-5D [EQ-5D; Euro quality of life 5 dimensions questionnaire, and North American Spine Society (NASS) satisfaction questionnaire]. MIS TLIF was associated with greater blood loss (mean 108.8 vs 33.0 ml, P < 0.001), longer operative times (mean 228.2 vs 101.8 minutes, P < 0.001), and longer length of hospitalization (mean 2.9 vs 0.7 days, P < 0.001). However, MIS TLIF was associated with a significantly lower reoperation rate (14.1% vs 1.4%, P = 0.004). In multivariate analyses, MIS TLIF, as opposed to MIS decompression alone, was associated with a superior ODI change, NRS back pain change, and NASS satisfaction. The authors concluded that for symptomatic, single-level degenerative spondylolisthesis, MIS TLIF was associated with a lower reoperation rate and superior outcomes for disability, back pain, and patient satisfaction compared with posterior MIS decompression alone. This finding may aid in the surgical decision-making when considering MIS for degenerative lumbar spondylolisthesis.

Contributed by Dr. Mazda K. Turel

Chohan MO, et al. Emerging pharmacologic targets in cerebral cavernous malformation and potential strategies to alter the natural history of a difficult disease. A review. JAMA Neurol 2019;76:492-500. doi: 10.1001/jamaneurol. 2018.3634.

The management of cerebral cavernous malformations (CCMs) remains an enigma for all. They may present in any part of the brain with the clinical presentation ranging from incidental detection to intracranial haemorrhage, seizures, or focal neurological deficits. The management options remain observation, anti-epileptic drugs, surgical resection, and stereotactic radiosurgery. The outcome of surgery remains good in hemispheric CCMs but dismal in deep seated locations. Similarly, the outcome is good in sporadic lesions but not in familial forms. In this article, Chohan et al., have presented the natural history of CCMs with its varied clinical presentation and management options, including their pros and cons. Emphasis has been on emerging pharmacological targets to alter the natural history of the disease. At present, there are multiple drugs from anti-angiogenic agents to anti-neoplastics to target the different genetic pathways. Unfortunately, the efforts have been met with little success as of now. The three most promising drugs have been propranolol, bevacizumab, and statins. Hopefully, these may prove to be of some benefit in the long term to decrease the bleed or seizure rate.

Contributed by Dr. Manjul Tripathi

Pelosi AJ. Personality and fatal diseases: Revisiting a scientific scandal. J Health Psych 2019. Doi: 10.1177/135910531882204.

Publication in the scientific literature has been a matter of great pride and innumerable biases. In this enlightening and entertaining article by Pelosi AJ, history has been revisited in a manner which seems like a court room saga. Commercial products are frequently contested in court because of their health hazards viz. cigarette smoking to lung cancer and mobile usage to the intracranial malignancies. It remains interesting to see how companies fund to distort medical evidences in their favour and how generations of human civilisation are forced to use or avoid certain goods in the absence of a level of evidence. One of the most controversial trials of its time was of Eysenck and Heidelberg regarding the personality traits of the human beings and risk of cancers. Another is cigarette smoking and risk of carcinogenesis or cardiovascular disorders. Large population based studies need proper statistical analyses and an absence of biases, which is seldom possible. Due to the same reasons, we sometimes find that natural oil products are bad for health, and a decade later, another study refutes the earlier notion. The onus lies on the scientists to provide the current picture with documentary evidences to avoid having their names in the black book.

Contributed by Dr. Manjul Tripathi

Zhou L, et al. Salt intake and prevalence of overweight/obesity in Japan, China, the United Kingdom, and the United States: the INTERMAP Study. Am J Clin Nutr 2019. doi: 10.1093/ajcn/nqz067.

This interesting article is to solidify the results of earlier studies defining the role of high salt intake and its associated morbidities. It is already proven that higher salt intake leads to a higher body mass index (BMI) and a higher risk of obesity/overweight. In this study, Zhou et al., have tried to identify the role of high salt intake in reference to relative risks of obesity/overweight and long term morbidities, obviating the flaws in the previous studies in different countries on a large population base. In different ethnic populations, 1g/day extra salt intake was associated with 21-29% higher risk of obesity/overweight. Higher salt intake is indirectly linked to an excessive thirst and a higher energy intake, further worsening this vicious cycle. However, this risk factor is independent of the energy intake. Such reports are especially important for the populations who are shifting from their traditional staple diet to junk foods, which are inherently high on carbohydrates and salt.

Contributed by Dr. Manjul Tripathi

Heit JJ, et al. Arterial-spin labeling MRI identifies residual cerebral arteriovenous malformation following stereotactic radiosurgery treatment. J Neuroradiol 2019. doi: 10.1016/j.neurad. 2018.12.004.

The primary objective in the management for arteriovenous malformations is obliteration of the nidus. AVM favours the neurosurgical principle of 'all or none', hence a partially obliterated nidus is never a goal, as it may increase the chances of bleed. The digital subtraction angiogram (DSA) remains the radiological modality of choice for ensuring a complete obliteration in view of its dynamic and more sensitive nature in comparison to the MRI techniques. Even when it fails to show any nidus, an early draining vein is a sign of some residual disease, which still poses a risk of bleed. In this article, the authors have cross checked the sensitivity and specificity of arterial spinal labelling (ASL) MRI techniques to identify nidus obliteration with subsequent DSA findings and inter observer variation in the reporting. The authors report ASL as a highly sensitive and specific radiological tool for the confirmation of nidus obliteration. This finding has a significant impact on the management of AVM patients, especially in those who have undergone radiosurgery. DSA remains an invasive and uncomfortable investigation for the patients and occasionally carries the risk of serious complications. If better and confirmatory MRI tools are available, the need of DSA can be negated, further increasing the patient's comfort and the physician's trust.

Contributed by Dr. Manjul Tripathi

Editorial. An app a day is only a framework away. Lancet Dig Health 2019. doi: 10.1016/S2589-7500 (19) 30031-7.

At present, we live in a digital world where smartphones have gradually replaced many humane needs. For every problem, we search google at least for once and sometimes even argue with the experts in that field citing our searched results. In this editorial based on three articles on the usage of smartphone apps in the health care, the results are both encouraging and alarming. The Lancet Digital Health has mentioned nearly 300,000 mobile apps for different medical ailments and health related issues. They not only guide the patients in deciding the management but also solidify their presence in the stock market with monetary gains. On the one hand, these ready apps are available at places where the health facilities are minimal, patients avoid face-to-face contacts, and the expenses are an issue. On the other hand, apps are not based on high quality clinical evidence. Majority of these apps, barring only a few exceptions, suffer from high efficacy and privacy concerns as the data is shared with a third party companies such as facebook. I have personally evaluated neurosurgery apps in a critical analysis (Tripathi M, et al. Neurosurgery apps: novel knowledge boosters. True Neurosurg 2014) and found that they add on to the confusion in the patient's minds and physicians cannot rely them in the absence of a solid scientific platform. Though easy to use, the results are perplexing and do not obviate the need for a doctor.

Contributed by Dr. Manjul Tripathi

Stephen LJ, et al. Management of epilepsy in women. Lancet Neurol 2019;18:481-91.

In comparison to a man with epilepsy, the life of a woman is no better. In this review article, Linda J Stephen, et al., reviewed the literature on the management of epilepsy in women, especially with respect to their reproductive health and social well being. The prevalence of females suffering from epilepsy is 6.85 cases per 1000 and a significant proportion suffer from catamenial epilepsy (a seizure during certain periods of menstrual cycle, which happens in around a third of women with epilepsy). This evidence based article presents an evidence based recommendation for female subjects in different stages of their life pertaining to menstrual cycle, contraception, fertility, parenthood, social and volitional choices and risk assessment for associated factors such as psychological needs. It is alarming to note that the majority of these female subjects have lesser awareness than the general population for contraception and the chances of injuries to their kids. Social platforms and general physicians should be on the forefront of managing this issue with better clarity in their own minds, as these patients seldom approach the specialists for such an important issue.

Contributed by Dr. Manjul Tripathi

Lehrer S, et al. Allergy may confer better survival on patients with gliomas. Clin Neurol Neurosurg 2019 doi: 10.1016/j.clineuro. 2018.12.021.

Gliomas continues to have a grim prognosis and this fact has remained the same in the last 3 decades. Though it is known that the presence of allergy confers a lower susceptibility to the development of a glioma, whether or not the same could confer a survival benefit too, is not clear. To evaluate the same, the authors studied hospital records of 526 patients harbouring a glioma. They found that patients with a history of allergy indeed had a survival advantage. This was independent of 1p, 19q co deletion, TP53 mutation etc. The underlying mechanisms for this interesting phenomenon remains unclear. One of the suggested causes include a cross reactivity of glioma antigens and allergens. The study obviously opens up a new avenue in glioma research.

Contributed by Dr. Ashish Aggarwal

Passeri T, et al. Spontaneous regression of meningiomas after interruption of nomegestrol acetate: A series of three patients. Acta Neurochir (Wien) 2019 doi: 10.1007/s00701-019-03848-x.

There is an association between sex hormones and the occurence and growth of meningiomas. This fact is supported by observations like: A female preponderance in meningiomas, the presence of intra-tumoral progesterone receptors, and dynamic changes in the tumor size during pregnancy. Therefore, it is only logical to think that progesterone agonists will stimulate the meningioma growth and discontinuation of these drugs should regress the tumor size. The authors studied three female patients having an intracranial meningioma, who were taking the drug, nomegestrol acetate (NOMAC). This drug is a derivative of 19-norprogesterone and has a strong action on the progesterone receptors. These patients were taking the drug for a minimum period of 20 years at the dosage of 5 mg per day. The authors measured the tumor volumes in all patients from MRI DICOM (magnetic resonance imaging-digital imaging and communications in medicine) images using the Carestream ® software. The drug was stopped in all the three patients and serial MRIs were performed after that. Tumor shrinkage was observed to a variable degree in all the three patients starting as early as 4 months. The authors conclude that since this drug is widely prescribed, further studies are needed to establish this relationship with a meningioma.

Contributed by Dr. Ashish Aggarwal

Bongetta D, et al. Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment. Clin Neurol Neurosurg 2019 doi: 10.1016/j.clineuro.2018.11.009.

Obesity has become a leading healthcare problem in many parts of the world. If the medical management fails, patients of morbid obesity are often subjected to bariatric surgery to control the excess body weight. This surgery has got its own share of complications, including those involving the central and peripheral nervous systems. In this analysis, the authors have analyzed 77 previous studies. The complications and pathological mechanisms have been grouped under 3 headings. Changes in intracranial pressure (ICP) include raised ICP, overdrainage and cerebrospinal fluid fistulae. Deficiency of various macro- and micro-nutrients may lead to peripheral neuropathy, myelo-encephalopathy, neural tube defects and weakening of spinal bony structure. Under autonomic and endocrine disturbances, the authors have mentioned orthostatic intolerance and alterations in the levels of various pituitary hormones. This study thus highlights a lesser known and discussed aspect of ever increasing trend for undergoing bariatric surgery.

Contributed by Dr. Ashish Aggarwal

Ou Y, et al. A comparative study of chronic subdural hematoma in three age ranges: Below 40 years, 41-79 years, and 80 years and older. Clin Neurol Neurosurg 2019 doi: 10.1016/j.clineuro.2019.01.018.

With an increasing proportion of geriatric population all over the world, the incidence of chronic subdural hematoma (CSDH) is bound to increase. The authors pulled out data of 1118 patients of CSDH and divided them in three age groups: ≤40 years, 41–79 years and ≥80 years. The percentage of patients in these age groups were 8.3%, 77.6% and 14.1%, respectively. Male patients predominated in all three age groups. As expected, the occurrence of co-morbidities like cardiac disease, diabetes etc., was more in the ≥80 years group. More than half of the patients in each group had a history of head trauma. Antiplatelet use was found in nearly 12% of the patients in group 2 and 3. Presence of an arachnoid cyst and installation of a ventrioculoperitoneal shunt was found as a risk factor in patients ≤40 years. The preoperative hematoma volume was biggest in patients ≥80 years. The reoperation rates were not statistically different amongst the three age groups. The use of anti-thrombotic agents did not alter the reoperation rates. The final outcome was poorer in patients aged ≥80 years.

Contributed by Dr. Ashish Aggarwal

Alizadeh R, et al. Human olfactory stem cells: As a promising source of dopaminergic neuron-like cells for treatment of Parkinson's disease. Neurosci Lett 2019. doi: 10.1016/j.neulet.2018.12.011.

Parkinson's disease is a neurodegenerative disorder characterised by a deficiency of dopamine due to the degeneration of dopaminergic neurons in the substantia nigra. To treat this disease, various approaches have been tried in the past, including medical therapy, deep brain stimulation etc., Replacing the degenerated neurons by stem cells is a promising therapy. In the present study, the authors have demonstrated that olfactory ecto-mesenchymal stem cells (OE-MSC) could differentiate into dopamine producing neurons, in vitro. They isolated olfactory mucosa from tiny biopsy materials. This was followed by multiple steps to make these cells differentiate into dopamine (DA) producing neurons in the presence of neurotropic factors. Combining four neurotropic factors sonic hedgehog (SHH), fibroblastic growth factor (FGF)8, glial cell-line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) with olfactory ectomesenchymal stem cells (OE-MSCs), the authors demonstrated in vitro maturation of these cells into DA neuron-like cells. The next logical step will be to demonstrate the efficacy of these cells in vivo.

Contributed by Dr. Ashish Aggarwal

Hallikainen J, et al. Periodontitis and gingival bleeding associate with intracranial aneurysms and the risk of aneurysmal subarachnoid hemorrhage. Neurosurg Rev 2019 doi: 10.1007/s10143-019-01097-1.

Rupture of intracaranial aneurysms (IAs) entail a high morbidity and mortality. On the other hand, even the treatment of unruptured IAs is not without complications. So, a method is required to estimate the risk of rupture in IAs. Since, aneurysmal formation and subsequent rupture is a multifactorial process, many cases of IAs cannot be explained by the known risk factors. In a quest to discover novel risk factor, the authors studied the relationship of periodontitis and gingival inflammation in IA formation and rupture. This study was performed in three sequential steps: As a first step, the authors recorded the prevalence of periodontitis and gingival inflammation in 89 patients of IA. Subsequently, as the step two, a case control study was done comparing these patients with controls from the same geographic location. The authors found an increased prevalence of periodontitis in IA patients as compared to the controls. As a third step, the patients of periodontitis were prospectively followed up for the development of IAs and they found an increased risk of SAH. The authors advocated further studies to establish the etiological role of periodontitis and IAs.

Contributed by Dr. Ashish Aggarwal

Trivedi DK, et al. Discovery of volatile biomarkers of Parkinson's disease from sebum. ACS Cent Sci 2019. doi: 10.1021/acscentsci.8b00879.

Since antiquity, physicians have used odors to diagnose specific diseases. Joy Milne had a unique ability to detect PD in her husband by a unique PD odor. This is postulated by the presence of some unique compounds in the sebum of PD patients. The authors here tried to identify and quantify such compounds to enable an early detection of PD. Sebum was collected from upper backs of PD cases and controls. This was subjected to thermal desorption − gas chromatography − mass spectrometry (TD − GC − MS) and various compounds were identified. The study group consisted of PD patients on drugs, drug naïve PD patients and controls. One of the compounds found was 3,4- dihydroxy mandelic acid, which is a metabolite of dopamine. Further, a mixture of nine compounds was described as having the smell typical of PD. A compound, perillic aldehyde, was significantly lower, and eicosane was significantly higher in PD patients than controls. There was no difference between PD patients on drugs and drug naïve PD patients. The authors advocate further studies to characaterize the PD volatilome.

Contributed by Dr. Ashish Aggarwal

Alptekin O, et al. Stereotactic accuracy and frame mounting: A phantom study. Surg Neurol Int 2019; doi: 10.25259/SNI-88-2019.

In this interesting study, the authors have tried to find out whether an asymmetrical mounted frame influences the accuracy of stereotactic lead implantation. They used watermelon as the phantom and Leksell frame was mounted over it in 3 different positions: Symmetrically parallel to Reidl's lines, rotational deviated mounting –18° rotation to the right side of the phantom, and lateral tilted mounting –10° lateral tilt. The deep brain stimulation (DBS) lead was pre-implanted and fixed with glue, and MRI was taken on the non-stereotactic phantom. Then, stereotactic computed tomograms were taken in three different mounted positions. Three different softwares were used to fuse and calculate XYZ co-ordinates (Framelink 5.4.1, Framelink Cranial, Brain lab iPlan). Manual calculations were also done by 2 different observers. It was found that the X and Y axis co-ordinates do not show much error (less than 1.0 mm) but the Z axis coordinates show a significant error (more than 1.3 mm) in asymmetrical mounted frames. Also, the error in Z axis coordinates was more with manual calculations than with the software. Errors could be minimized by using a stereotactic scan for registration, rather than a non-stereotactic scan (MRI).

Contributed by Dr. Navneet Singla

Depauw PRAM, et al. The significance of intra-abdominal pressure in neurosurgery and neurological diseases: A narrative review and a conceptual proposal. Acta Neurochir 2019;161:855-64.

Increased intra-abdominal pressure (IAP) has been implicated in dysfunction of various organs but its role in neurological disorders and during neurosurgical procedures is understated. IAP is uniformly distributed and can be measured from any of the intra-abdominal cavities but the most frequently used method is through the urinary catheter. Abdominal compartmental syndrome has been defined as sustained increase in IAP more than 12 mmHg. Various articles were searched from pubmed using search items like 'intra-abdominal pressure AND neurosurgery', 'intra-abdominal pressure AND spine surgery', 'intra-abdominal pressure AND traumatic brain injury', 'intra-abdominal pressure AND hydrocephalus', 'intra-abdominal pressure AND idiopathic intracranial hypertension' from 1918 to 2018, and also by screening the references of the identified articles. Two pathways have been proposed by which increased IAP can cause an increased intracranial pressure (ICP): One is through valve-less spinal venous plexus and intracranial veins, and secondly through upward diaphragmatic shift causing an increased intra-thoracic pressure, thus, reducing the venous drainage from the central nervous system. Current literature suggests that IAP can play an important role in the management of idiopathic intracranial hypertension (IIH), traumatic brain injury (TBI) and hydrocephalus. Increased knowledge of the role of IAP in ICP can also provide safety in spinal and posterior fossa surgeries that require the patient to be in a prone position.

Contributed by Dr. Navneet Singla

Epstein NE. A comparison of kyphoplasty, vertebroplasty, or non-surgical treatment of traumatic/atraumatic osteoporotic vertebral compression fractures: A short review. Surg Neurol Int 2019; doi: 10.25259/SNI-123-2019.

In this review article, the author compared vertebroplasty, kyphoplasty and non-surgical treatment (NST) in the management of traumatic/atraumatic osteoporotic vertebral compression fractures (OVCFs). Up to 40% of these fractures may exhibit persistent pain which may warrant some sort of surgical intervention like vertebroplasty (V) or kyphoplasty (K). Various studies give different views regarding the superiority of V over K, or vice versa, in attaining vertebral height and correction of the kyphotic angle but all agree about their definite advantage over NST. The leakage of cement was comparable in V and K. The frequency of adjacent level fractures (ALF) is more in V or K than NST. The procedural time is more with K as compared to V. The 30 day mortality and morbidity data is also comparable between the three treatment modalities. In conclusion, both the procedures give better pain relief, better quality of life scores and better restoration of vertebral body height as compared to NST but adjacent level fractures and recurrent OVCF are more with the surgical patients. Overall, there is little difference between V and K in the long run.

Contributed by Dr. Navneet Singla

Park YK, et al. Risk factors for recurrence and retreatment after endovascular treatment of intracranial saccular aneurysm larger than 8 mm. Acta Neurochir 2019;161:939-46.

In this retrospective study, the authors have analyzed the risk factors in the recurrence of intracranial saccular aneurysms greater than 8 mm in size in patients who underwent endovascular coiling. A total of 171 patients with a mean age of 59 yrs were included in the study. 119 underwent coiling without a stent and 52 underwent stent- assisted coiling. The total recurrence and retreatment rates were 25.7% (44/171) and 10.5% (18/171), respectively, over a 42- month median follow-up duration. According to the aneurysm location, the paraclinoid internal carotid artery ICA aneurysm showed the lowest (12.5%) and the distal ICA aneurysm showed the highest recurrence rate (42.1%). On multivariate analysis, four variables remained significant: A larger aneurysm size, rupture status, an incomplete occlusion and a low dome-to-neck ratio. The patients were divided into 4 groups according to stent-assisted coiling (SAC) and packed density of coils (PD). The recurrence rate for the no-stent with low PD (<17.5%) group was 50% (14/28). It was 37.5% (6/16) for the stent-assisted coil (SAC) with low PD group, 22.0% (20/91) for the no-stent with high PD group and 11.1% (4/36) for the SAC with high PD group. In conclusion, larger ruptured aneurysms with a low dome-to-neck ratio with incomplete occlusion have more chances of recurrence and it can be reduced by stent assisted coiling.

Contributed by Dr. Navneet Singla

Fekete G, et al. Surgical treatment of tethered cord syndrome - comparing the results of surgeries with and without electrophysiological monitoring. Child's Nerv Syst 2019;35:979-84.

The authors studied the effect of intraoperative electrophysiological monitoring (IOM) on the short and long-term outcomes of surgical treatment of tethered cord syndrome. A total of 102 procedures were done in 91 patients, 70 with monitoring and 32 without. The rate of reoperation was 19.6% with a significantly lower rate of reoperation in the electrophysiological group (8.6% versus 23.8%). The overall risk for early neurological deterioration was 7.8% (5.7% in IOM group vs 12.5% in the other). Permanent surgery related deficits were also more in the non monitored group (9.4% versus 2.9%). At an average follow up of 45.72 months, 17.7% of the patients showed progression. It was also lower in the IOM group (11.3% versus 30.8%). Out of 44 procedures in asymptomatic patients, 4.5% developed early neurological worsening (0% in IOM group versus 8.7% in non monitored group). In rest of the 58 procedures in patients with neurological deficits, 5.2% developed new deficits, 4.1% in the IOM versus 11.1% in the non-IOM group. In conclusion, the risk of new neurological deficits can be reduced by IOM and it also helps in reducing the long term disease progression and re-procedure rates.

Contributed by Dr. Navneet Singla

Vleggeert-Lankamp CLA, et al. The NECK trial: Effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; A double-blinded randomized controlled trial. Spine J 2019;19:965-75.

In NECK (Netherlands Cervical Kinematics) trial, the authors have analysed the effectiveness of three procedures: Arthroplasty with artificial disc (ACDA), fusion using cervical plate (ACDF), and no implant (ACD), after anterior cervical discectomy for cervical radiculopathy. They divided 109 patients randomly and equally in 3 groups, 98 out of which could complete 104 weeks follow up; 32 in ACDA, 34 in ACDF and 32 in ACD. The primary outcome measure was neck disability index (NDI), a modification of Oswestry low back pain index and the secondary outcome measure was the visual analogue scale (VAS) neck pain, VAS arm pain, short form 36 (SF36), Euro quality of life 5-dimensions E(Q-5D), patients' self-reported perceived recovery, radiographic cervical curvature and adjacent segment degeneration parameters at baseline and until two years after surgery. The NDI decreased significantly from 41 to 47 points at baseline to 19 +/- 15 in the ACD group, 19 +/- 18 in the ACDF group, and 20 +/-22 in the ACDA group after surgery to 19 − 20 points after 1 year in all three groups (p<.001). Neck pain and back pain VAS also improved significantly after 1 year in all treatment groups and persisted at a 2-year interval. The Likert perceived recovery scale, EQ-5D and SF-36 all showed improvements in scores without any statistically significant difference. There was no statistically significant difference in the three groups in the alteration of cervical curvature. In conclusion, arthroplasty did not show superiority over ACDF, and discoidectomy alone without implantation can be an alternative modality in single level cervical disc disease.

Contributed by Dr. Navneet Singla

Hollingworth, et al. How is vasospasm screening using transcranial Doppler associated with delayed cerebral ischemia and outcomes in aneurysmal subarachnoid hemorrhage? Acta Neurochir 2019;161:385-92.

The authors have tried to see whether screening for vasospasm using transcranial Doppler (TCD) in aneurysmal subarachnoid haemorrhage (SAH) results in any improvement in the patient outcome. They used United Kingdom and Ireland Subarachnoid Haemorrhage (UKISAH) Registry to obtain data from the screening centres which use TCD, and also data from non-screening centres which do not use TCD as a screening tool for vasospasm and further development of diffuse cerebral ischemia (DCI). A total of 2028 patients were taken, who were treated within 3 days of ictus, 1065 from non-screening centres and 963 from screening centers. Surprisingly, more patients from the non-screening group had better Glasgow Outcome Scale (GOS) scores. Overall, 79.5% patients in the non-screening group had a favourable outcome (GOS 4 and 5) as compared to 67.2% in the screening group. Also, fewer patients were discharged in a persistent vegetative state (0.8% vs 2.4%; P value = 0.003) or a severely disabled state (12.8%vs 22.3%; P value = 0.001) in the non-screening group. Therefore, the study shows that vasospasm picked up on TCD perhaps invites over-aggressive treatment that may not be necessary and the poorer outcome could actually result from these aggressive management strategies.

Contributed by Dr. Navneet Singla

Dremmen MHG, et al. Cavum septum pellucidum in the general pediatric population and its relation to surrounding brain structure volumes, cognitive function, and emotional or behavioral problems. Am J Neuroradiol 2019;40:340-6.

The area between the two lateral ventricles houses a cerebrospinal fluid (CSF) filled compartment named the cavum septum pellucidum (CSP). This cavity usually closes within 5 months after birth. Its persistence or enlargement has been linked, in some studies, to psychiatric disorders. The authors attempt to examine the relationship between the CSP and volumes of various brain structures and its clinical correlation with cognition and childhood behaviour. A large cohort of more than a thousand children was taken wherein their MR scans were evaluated for the presence and the length of a persistent CSP and brain volumes. A large CSP was seen in about 5% of the children and this group had a larger corpus callosum, greater thalamic and total white matter–to–total brain volume ratio, and smaller lateral ventricle volumes. No association was established between CSP and cognitive function or emotional and behavioural problems, and hence, a large CSP was acquitted of any significant clinical implications.

Contributed by Dr. Chirag K Ahuja

Brott TG, et al. Carotid Stenosis Trialists' Collaboration. Long-term outcomes of stenting and endarterectomy for symptomatic carotid stenosis: A preplanned pooled analysis of individual patient data. Lancet Neurol. 2019 doi: 10.1016/S1474-4422 (19) 30028-6.

Carotid revascularization remains the mainstay of treatment for symptomatic carotid stenosis. Carotid artery stenting (CAS), even though less invasive, bears the increased risk of periprocedural stroke than carotid endarterectomy (CEA) in the short term. The present study aims to evaluate the long-term follow-up of patients treated by one of these procedures. A pooled analysis of around 5000 patient-level data, acquired from the four largest randomised controlled trials assessing the relative efficacy of CAS and CEA for treatment of symptomatic carotid stenosis (Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy trial, International Carotid Stenting Study, and Carotid Revascularization Endarterectomy versus Stenting Trial) was done. The risk of ipsilateral stroke along with the composite risk of stroke or death was slightly higher for CAS than CEA; however, it was not significantly different, suggesting a robust clinical durability for both the treatments. The similarity of the postprocedural rates suggest that improvements in the periprocedural safety of CAS could provide similar outcomes of the two procedures in the future.

Contributed by Dr. Chirag K Ahuja

Licher S, et al. Lifetime risk of common neurological diseases in the elderly population. J Neurol Neurosurg Psychiatry 2019;90:148-56.

The immense risk of neurological disease has a significant bearing on lifestyles across all ages, especially in the elderly subjects. The authors attempt to quantify the burden of common neurological disease in older adults in terms of lifetime risks, including their co-occurrence and preventive potential, within a competing risk framework. The sample from Rotterdam Study was used and the lifetime risk of dementia, stroke and  Parkinsonism More Details between 1990 and 2016 was assessed. 12,102 individuals aged ≥ 45 years, free from these diseases at baseline, were enrolled. During follow-up of up to 26 years, 1489 individuals were diagnosed with dementia, 1285 with stroke and 263 with parkinsonism and 438 (14.6%) with multiple diseases. Women were almost twice as likely as men to be diagnosed with both stroke and dementia during their lifetime. Preventive strategies could thus be adopted that could theoretically reduce the lifetime risk for developing these diseases.

Preventive interventions at population level should thus be prioritized to reduce the burden of common neurological diseases in the ageing population.

Contributed by Dr. Chirag K Ahuja

Funatsu N, et al. Vascular wall components in thrombi obtained by acute stroke thrombectomy: Clinical significance and related factors. J Neurointerv Surg. 2019;11:232-6.

Mechanical thrombectomy (MT) yields clots with variable compositions including vascular wall components (VWCs) in the form of collagen fibers. This study tried to clarify the factors associated with VWCs in the retrieved thrombi. All consecutive acute stroke patients who underwent MT over a 30-month duration in the author's institute were enrolled and their clots were assessed histopathologically. VWCs were defined as banded collagen fibers with a distinct boundary observed at the rim or outside of the retrieved thrombi. 150 specimens from 101 patients were investigated. VWCs were observed in 24 specimens (16%) from 22 patients. A low proportion of erythrocyte components, a high frequency of the devices reaching the M2/P2 segment and a high number of device passages were associated with VWC positive thrombi. Successful recanalization (Treatment in Cerebral Ischemia stage ≥ 2b) tended to be less frequent in patients with VWC positive thrombi than in those without. They concluded that the histopathology of occlusive thrombi, arterial sites where the devices reached, and the number of device passages, might affect the presence of VWCs in retrieved thrombi, which logically would increase the chances of arterial wall injury.

Contributed by Dr. Chirag K Ahuja

McDougall CM, et al. Fifty shades of gradients: Does the pressure gradient in venous sinus stenting for idiopathic intracranial hypertension matter? A systematic review. J Neurosurg 2018 doi: 10.3171/2017.8.JNS17459.

Venous sinus stenting (VSS) for idiopathic intracranial hypertension (IIH) is still not well established. This systematic review attempts to identify the subsets of patients with IIH who might benefit from VSS based on the pressure gradients of their venous sinus stenoses. MEDLINE/PubMed database was searched for studies reporting venous pressure gradients across the stenotic segment of the venous sinus, pre- and post-stent pressure gradients, and clinical outcomes after VSS. A total of 186 patients were included. Patients who had favourable outcomes had higher mean pressure gradients and higher changes in pressure gradients after stent placement compared with those with unfavourable outcomes. The post-stent pressure gradients between the 2 groups were not significantly different. In a multivariate stepwise logistic regression, the change in pressure gradient with stent placement was found to be an independent predictor of a favourable outcome. Using a pressure gradient of 21 as a cut-off, 94.2% of patients with a gradient >21 achieved favourable outcomes, compared with 82.0% of patients with a gradient ≤21 (P = 0.022).

In conclusion, there appears to be a relationship between the pressure gradient of venous sinus stenosis and the success of VSS in IIH, though randomized trials would surely be a better proof.

Contributed by Dr. Chirag K Ahuja

Vasco Vanhala, et al. Prevalence of schizophrenia in idiopathic normal pressure hydrocephalus. Neurosurgery 2019;84:883-9.

Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and potentially treatable neurodegenerative disease affecting elderly people. It is characterized by gait impairment, dementia and urinary disturbances and cranial imaging uncovers a ventricular enlargement in them. Schizophrenia (SCZ) may sometimes have similar imaging findings. This study aimed at deciphering whether the treatment strategy needed to change in concurrent iNPH and SCZ. NPH registry was used as the databank and all medical records of the 521 iNPH patients were retrospectively analyzed. A total of 16 (3.1%) iNPH patients suffering from comorbid SCZ were identified. The prevalence of SCZ among the iNPH patients was significantly higher compared to the general population. All iNPH patients with comorbid SCZ were CSF shunted and 12 (75%) had a clinically verified shunt response 3 to 12 months after the procedure. The CSF shunt response rate did not differ between patients with and without comorbid SCZ. It was concluded that SCZ seems to occur 3 times more frequently among iNPH patients compared to the general population of the same age. The outcome of treatment was not affected by comorbid SCZ, and therefore, iNPH patients suffering from comorbid SCZ should not be left untreated.

Contributed by Dr. Chirag K Ahuja

GBD 2016 Epilepsy Collaborators. Global, regional, and national burden of epilepsy, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019 doi: 10.1016/S1474-4422(18)30454-X.

Epilepsy has been a major cause of morbidity and health loss across the globe. The investigators aimed to quantify the health loss due to epilepsy by age, sex, year, and location using data from the Global Burden of Diseases, Injuries, and Risk Factors Study. 195 countries were surveyed from 1990 to 2016. Data from vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy largely came from population representative surveys. In 2016, there were 45.9 million patients with all-active epilepsy with peaks at 5-9 years and >80 years of age. Age-standardised prevalence of active idiopathic epilepsy, mortality rates and disability-adjusted life years (DALYs) were greater in men than women. Between 1990 and 2016, there was a non-significant (6.0%) change in the age-standardised prevalence of idiopathic epilepsy, but a significant decrease in age-standardised mortality rates and age-standardised DALY rates. They concurred that epilepsy still remained an important cause of disability and mortality despite a decrease in the disease burden from 1990 to 2016. Improved access to existing treatments in low-income countries and development of new effective drugs worldwide is are likely to impart sizeable gains in reducing the global burden of epilepsy.

Contributed by Dr. Chirag K Ahuja and Dr. Ravi Yadav

Zonner SW, et al. Oculomotor response to cumulative sub concussive head impacts in US high school football players. JAMA Ophthalmol 2018 doi: 10.1001/jamaophthalmol.2018.6193.

Repetitive sub concussive head impacts in sports may remain asymptomatic for long durations but bear a significant potential to cause insidious neurological deficits. Near point of convergence (NPC) values have shown to reflect a subclinical neuronal damage; however, the pattern of NPC changes associated with sub concussive head impacts is not clearly defined. In this interesting prospective case series study of 12 US varsity high school football players, NPC response to recurring sub concussive head impacts was assessed. An accelerometer-embedded mouth guard measured the head impact frequency and magnitude from all practices and games. During the 6 games, players wore chest-strap heart rate monitors to record their heart rate and estimate their excess post exercise oxygen consumption, accounting for the possible physical exertion effects on NPC values. This longitudinal case series study suggested that NPC could be perturbed over long term by sub concussive head impacts but may normalize over time, hence signifying the adaptational capacity of the oculomotor system.

Contributed by Dr. Aastha Takkar

Staudi S, et al. Robot-assisted gait training is not superior to intensive over ground walking in multiple sclerosis with severe disability (the RAGTIME study): A randomized controlled trial. Mult Scler 2019. doi: 10.1177/1352458519833901

The impact of rehabilitation on mobility of the patients of multiple sclerosis is indisputable. In this randomized controlled trial of 72 patients of progressive MS (expanded disability status scale score 6.0–7.0), the authors compared an advanced robot-assisted gait training (RAGT) with conventional therapy (CT) in terms of gait speed, mobility, balance, fatigue and quality of life. The patients were randomized to receive 12 training sessions over a 4-week period of RAGT or over ground walking therapy. At the end of treatment, both groups had a significantly improved gait speed with respect to the baseline. Most secondary outcomes did not demonstrate any significant differences at the end of the trial. RAGT was hence, not considered to be superior to CT in improving gait speed in patients with progressive MS and severe gait disabilities.

Contributed by Dr. Aastha Takkar

Madsen J, et al. Music synchronizes brainwaves across listeners with strong effects of repetition, familiarity and training. (Nature) Sci Rep 2019;9:3576.

Although much has been postulated, still less is known about the effects of music on human psychology. In this interesting article, the authors postulate that the engagement with music affects the inter-subject correlation of brain responses during listening. Three experiments with a total of 40 participants were carried out. Stimuli with excerpts of instrumental classical music composed in a familiar or unfamiliar style were provided and electroencephalogram (EEG) as well as electrooculography (EOG) were recorded. Across repeated exposures to instrumental music, the inter-subject correlation was found to be decreased for music of familiar style. Sustained inter-subject correlation, across exposures to music in an unfamiliar style, was more in the participants with formal music. This distinguishes music from other domains, where repetition has consistently been shown to decrease the inter-subject correlation. The study suggested that the listener engagement tends to decrease across repeated exposures of familiar music, but unfamiliar musical styles can sustain an audience's interest, in particular in individuals with some musical training.

Contributed by Dr. Aastha Takkar

Bonnan M, et al. Predictive value of conventional MRI parameters in first spinal attacks of neuromyelitis optica spectrum disorder. Mult Scler 2019. doi: 10.1177/1352458519834857.

Prognostic markers in neuromyelitis optica spectrum disorder (NMOSD) remain elusive. The authors retrospectively studied the correlation between conventional non-standardized magnetic resonance imaging (MRI) parameters, plasma exchange treatment, and clinical data obtained at nadir and recovery for their predictive importance. Sixty- nine Afro- Caribbean NMOSD patients with first attacks in the form of spinal cord involvement were assessed. All conventional MRI parameters were noted to correlate with the nadir and the residual Expanded Disability Status Scale (EDSS) in bivariate analysis. Surprisingly, gadolinium enhancement was not associated with the outcome. The authors concluded that specific pattern of lesions in conventional MRI data was differentially associated with the prognosis and residual EDSS. Hence, the presence of conventional lesions may require an early and prompt management

Contributed by Dr. Aastha Takkar

Abbound H, et al. Movement disorders in early MS and related diseases: A prospective observational study. Neurol Clin Pract February 2019;9:24-31.

Movement disorders in early multiple sclerosis (MS) and related demyelinating diseases have not been explored properly. In this study, sixty- six patients with MS were prospectively assessed for the presence of movement disorders. Each patient was interviewed by a movement disorder specialist who conducted a detailed examination and a standardized movement disorder survey. Eighty percent patients reported one or more movement disorders on the survey and 38.3% had positive findings on clinical examination. After excluding incidental movement disorders (e.g. essential tremor), 58.3% were thought to have demyelination-related movement disorders. The most common movement disorders in a descending order were restless legs syndrome, tremor, tonic spasms, myoclonus, focal dystonia, spontaneous clonus, fasciculations, pseudoathetosis, hyperekplexia, and hemifacial spasm. The movement disorder started 5 months following a relapse on an average, but in 8 patients, it was the presenting symptom of a new relapse or the disease itself. Spinal cord demyelination was the only statistically significant predictor of demyelination-related movement disorder. This study has uncovered that movement disorders are probably more common than previously thought even in early MS.

Contributed by Dr. Aastha Takkar

Cacciaguerra L, et al. Brain and cord imaging features in neuromyelitis optica spectrum disorders. Ann Neurol. 2019;85:371-84.

This cross sectional study was carried out in 116 patients of neuromyelitis optica spectrum disorders (NMOSD) and 65 age and sex matched multiple sclerosis (MS) patients to validate the imaging features in NMOSD. Typical brain lesions occurred in 50.9% of NMOSD patients, 72.2% had spinal cord lesions, 37.1% satisfied the 2010 McDonald criteria and none had cortical lesions. Fulfillment of at least 2/5 of the following factors: Absence of juxtacortical/cortical lesions, absence of periventricular lesions, absence of Dawson's fingers, presence of long transverse myelitis or presence of periependymal lesions along the lateral ventricles, discriminated NMO patients in both training and validation samples. Although up to 50% of NMO patients have no typical lesions and a relatively high percentage of them satisfy the MS criteria, several easily applicable imaging features may help in differentiating these two conditions.

Contributed by Dr. Aastha Takkar

Sadaka A, et al. Vitamin D and selenium in a thyroid eye disease population in Texas. Neuro-Ophthalmol 2019. doi: 10.1080/01658107.2019.1566382.

Nutritional deficiencies have been observed to be associated with thyroid eye disease (TED). The authors conducted a retrospective chart review of thirty five consecutive patients with clinical diagnosis of TED from 2016 to 2017. 20% of the patients were noted to have vitamin D deficiency, and 31% had vitamin D insufficiency. None of these patients were noted to have selenium deficiency. The authors suggested the need for further studies to justify selenium supplementation for patients with TED.

Contributed by Dr. Aastha Takkar

Diener HC, et al. Dabigatran for prevention of stroke after embolic stroke of undetermined source. N Engl J Med 2019;380:1906-17.

Cryptogenic strokes account for about 20-30% of all ischemic strokes and are considered to be embolic if a non-lacunar pattern of infarction is visible on cranial MRI and all the tests are negative. The authors in this randomized multicentre trial, called as RESPECT-ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) trial, compared dabigatran and aspirin in prevention of recurrent stroke in patients fulfilling the criteria for ESUS (embolic stroke of undetermined significance). Dabigatran (110 or 150 mg/day) was not found to be superior to aspirin (100 mg/day) in the prevention of recurrent stroke. While there was no major bleeding in the dabigatran group, non-major clinically relevant bleedings were more frequently observed.

Contributed by Dr. Sahil Mehta

Tabrizi SJ, et al. Targeting Huntingtin expression in patients with Huntington's disease. N Engl J Med 2019. doi: 10.1056/NEJMoa1900907.

Huntington's disease is a progressive neurodegenerative condition characterized by movement disorder, cognitive decline and behavioral issues. It is a trinucleotide repeat disorder in which CAG repeat expansion occurs in the huntingtin gene. At present, only symptomatic therapies are available. The authors in this phase 1-2a trial studied the safety profile and pharmacokinetics of IONIS-HTTRX(Ionis Pharmaceuticals, Inc. Huntington's disease) an antisense oligonucleotide designed to inhibit HTT messenger RNA. Patients in the early stage of Huntington's disease (classified by unified Huntington's disease rating scale total functional capacity score of 11-13) were enrolled in this multicenter trial. Intrathecal administration of this new drug, in escalating doses of 10-120 mg, was found to be safe with only grade 1-2 adverse events. The authors also found dose dependent reductions of mutant huntingtin protein in the cerebrospinal fluid. Large randomized clinical trials for the efficacy are needed to see whether the findings of this trial will translate into clinical benefit.

Contributed by Dr. Sahil Mehta

Pittock SJ, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med 2019. doi: 10.1056/NEJMoa1900866.

Eculizumab is a humanized monoclonal antibody, which prevents the cleavage of terminal complement C5 into C5a and C5b and prevents the formation of membrane attack complex. In this randomized double-blind PREVENT trial (A Randomized Controlled Trial of Eculizumab in AQP4 Antibody-positive Participants With NMO (PREVENT Study)], eculizumab was compared to a placebo and a concomitant low dose immunosuppressive therapy (75% patients). Patients who received eculizumab had a significantly lower risk of relapse as compared to those who received the placebo. However, there was no significant change in the disability progression, as measured by Expanded Disability Status Scale (EDSS). Higher rates of upper respiratory infection and headache were reported in the eculizumab group. One patient receiving concomitant azathioprine died of pulmonary empyema. However, the results cannot be applied to myelin oligodendrocyte glycoprotein (MOG) positive patients. Further trials with a large sample size are needed to assess the efficacy of eculizumab in disability progression.

Contributed by Dr. Sahil Mehta

Nelson PT, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): Consensus working group report. Brain 2019. doi: 10.1093/brain/awz099.

The authors have described a recently recognized disease entity called as LATE (limbic-predominant age-related TDP-43 encephalopathy) which shares the clinical and pathological features with Alzheimer's disease and frontotemporal lobar degeneration. LATE neuropathology is defined by stereotypical TDP-43 proteinopathy with or without coexistent hippocampal sclerosis pathology. Oldest Old (>80 years of age) are at the greatest risk of developing it. It mimics the clinical features of Alzheimer's disease (amnestic syndrome) albeit with a slower disease progression. However, the presence of co-morbid Alzheimer's pathology causes a more rapid clinical decline. Based on the anatomical distribution of TDP-43 pathology, a staging system has also been devised. Stage 1: amygdala only; stage 2:+ hippocampus; stage 3: +middle frontal gyrus. Five genes have been implicated namely GRN, TMEM106B, ABCC9, KCNMB2 and APOE. There is no molecule specific biomarker for LATE at present.

Contributed by Dr. Sahil Mehta

Ma H, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med 2019;380:1795-1803.

Currently, the time to initiate intravenous thrombolysis is limited to 4.5 hours after the onset of ischemic stroke. The authors, in this multicentre placebo controlled randomized clinical trial (EXTEND; EXtending the time for Thrombolysis in Emergency Neurological Deficits), enrolled patients who had hypoperfused but salvageable regions of brain, as detected by automated perfusion imaging. Patients were enrolled between 4.5 to 9 hours after the onset of stroke or after awakening with stroke (9 hours from the mid-point of sleep). The use of alteplase therapy between 4.5 to 9 hours of stroke onset with salvageable brain tissue resulted in a significantly higher percentage of patients with mild neurological deficits (mRS 0-1) with an absolute difference of 6% points. However, the alteplase group had higher chances of symptomatic intracranial haemorrhage compared to the placebo group. There was no difference in mortality between the two groups. The trial was terminated early in view of the positive results of the WAKE UP (MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset) trial.

Contributed by Dr. Sahil Mehta

Pijpers JA, et al. Acute withdrawal and botulinum toxin A in chronic migraine with medication overuse: A double-blind randomized controlled trial. Brain 2019;142:1203-14.

Chronic migraine is defined as headache days >15 days/month for >3 months, out of which >8 days should be migrainous. Medication overuse is a major risk factor for conversion of episodic migraine to chronic migraine. The authors in this single centre randomized trial studied the efficacy of botulinum toxin in chronic migraine with medication overuse as an add on to acute withdrawal of medicine for 3 months. 179 adults received either botulinum toxin A (BTX A, 155 units) or a placebo (saline plus 17.5 units BTX A to maintain blinding) followed by medication withdrawal on an out patient basis for 3 months. There was no significant difference between the two groups in terms of monthly headache days, measures of disability and quality of life. The limitations of this study are its small sample size, use of small amount of BTXA in the placebo group and early interpretation of the results.

Contributed by Dr. Sahil Mehta

Montalban X, et al. Placebo-controlled trial of an oral BTK inhibitor in multiple sclerosis. N Engl J Med 2019. doi: 10.1056/NEJMoa1901981.

Evobrutinib is a selective, covalent oral inhibitor of BTK that blocks B-cell activation and the release of cytokines. The authors in this randomized placebo controlled phase 2 trial compared evobrutinib and a placebo, dimethyl fumarate, as reference in patients with active relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) with superimposed relapses. There were significantly lesser number of gadolinium enhancing lesions with evobrutinib 75 mg once daily after 24 weeks of treatment compared to the placebo. However, lower or higher doses of the drug could not replicate the results. Moreover, there was no significant difference in the annualized relapse rate. Abnormalities in liver function tests were associated with higher doses of evobrutinib. Trials with a large sample size and larger duration of follow up are needed to evaluate the risks and benefits of this new oral drug in multiple sclerosis.

Contributed by Dr. Sahil Mehta

Poon MTC, et al. Influence of antiplatelet and anticoagulant drug use on outcomes after chronic subdural hematoma drainage. J Neurotrauma 2019. doi: 10.1089/neu.2018.6080.

The authors aimed to study the outcomes after drainage of chronic subdural hematoma (CSDH) in patients who were on antithrombotic drugs, either antiplatelets or anticoagulants, at presentation. Data of 353 patients who were on antithrombotic medications was retrieved from a previous multicentric prospective study. A gradual reduction in the risk of recurrence for patients during the 6 weeks post-CSDH surgery was observed. The use of antiplatelet or anticoagulant drug did not influence the risk of CSDH recurrence or persistent/worse functional impairment. The risk of bleed recurrence was not affected by delaying the surgery after cessation of the antiplatelet drug. The risk of thromboembolic event was more in the group who were on antithrombotic medications as compared to those who were not (3.3% vs 0.9%). Hence, patients on an antithrombotic drug pre-operatively were at a higher risk of thromboembolic events with no excess risk of hematoma recurrence or worse functional outcome after CSDH drainage. The authors concluded that early surgery and early antithrombotic initiation should be considered in those at a high risk of thromboembolic events.

Contributed by Dr. Kanwaljeet Garg

Kamran S, et al. Predictors of decompressive hemicraniectomy in malignant middle cerebral artery stroke. Neurosurg Rev 2019;42:175-81.

The authors wanted to study the factors that predict the need for decompressive hemicraniectomy (DC) in patients with malignant middle cerebral artery (MMCA) stroke in order to facilitate patient selection for DC. This study was a retrospective multicenter study of patients referred for DC based on the criteria suggested in previous randomized control trials of DC in MMCA stroke. The patients who underwent DC were compared to those who survived without surgery. Two hundred and three patients with MMCA strokes were identified: 137 underwent DC, 47 survived without DC, and 19 refused surgery and died. Multivariate analysis identified the following factors determining DC in MMCA stroke: age < 55 years, MCA with involvement of additional vascular territories, septum pellucidum displacement ≥7.5 mm, diabetes, infarct growth rate, and temporal lobe involvement. The presence of these risk factors identifies those MMCA stroke patients who may require DC. Bootstrapping analysis indicated the validity of the model to predict the outcome in general population.

Contributed by Dr. Kanwaljeet Garg

Nguyen T, et al. Surgery versus stereotactic radiosurgery for the treatment of multiple meningiomas in neurofibromatosis type 2: illustrative case and systematic review. Neurosurg Rev 2019;42:85-96.

In patients with neurofibromatosis type 2 (NF2), the multiplicity of meningiomas renders complete resection of all developing lesions infeasible. Stereotactic radiosurgery (SRS) may be a viable non-invasive therapeutic alternative to surgery. A total of 50 patients (27 radiosurgical and 23 surgical) were studied in this systematic review. Local tumor control was achieved in 81.5% patients (n = 22) and distal control was achieved in 51.8% of the patients who received gamma knife radiosurgery. No patient experienced malignant transformation (average follow up – 90 months). Complications in the SRS-treated cohort were reported in 9 patients (33%). Eight patients (29.6%) died due to the disease progression. Six patients experienced treatment failure and required further management. For NF2 patients treated with surgery, 11 patients (48%) showed tumor recurrence and 10 patients (43.5%) died due to neurological complications. The authors concluded that SRS may be a safe and effective alternative for NF2-associated meningiomas without the risk of malignant transformation.

Contributed by Dr. Kanwaljeet Garg

Schuss P, et al. Risk factors for shunt dependency in patients suffering from spontaneous, non-aneurysmal subarachnoid hemorrhage. Neurosurg Rev 2019;42:139-45.

Patients presenting with spontaneous, non-aneurysmal subarachnoid hemorrhage (SAH) achieve better outcomes compared to patients with aneurysmal SAH. Nevertheless, some patients develop shunt-dependent hydrocephalus during the course of the treatment. The authors aimed to identify the factors determining shunt dependency after non-aneurysmal SAH in this study involving 131 patients. Patients were divided into two groups, as per the distribution of cisternal blood, into: patients with perimesencephalic SAH (pSAH) versus non- perimesencephalic SAH (npSAH). Overall, 14% of the patients required a shunt in the study. The patients with npSAH required a shunt more often than the pSAH patients and the difference was statistically significant. The other predictors which significantly increased the need of a shunt were presence of acute hydrocephalus, presence of intraventricular hemorrhage, presence of clinical vasospasm, and anticoagulant usage prior to SAH. In the multivariate analysis, however, it was the acute hydrocephalus that turned out to be the only significant and independent predictor for shunt dependency in these patients.

Contributed by Dr. Kanwaljeet Garg

Ituarte F, et al. Posterior thoracolumbar instrumented fusion for burst fractures: A meta-analysis. Clin Spine Surg 2019 doi: 10.1097/BSD.0000000000000763.

This meta-analysis was performed to elucidate if the current body of literature supported one posterior spinal fusion fixation method for burst fracture over others to minimize the rate of implant failure and progression of posttraumatic kyphosis. A total of 23 publications were included into this study. The types of instrumentation were divided into 7 tiers- depending on the number of vertebral levels fixed superior and inferior to the fractured vertebrae, and whether or not screw was put in the fractured vertebrae (1 or 2 level up and down with or without fractured level screw). The group with instrumentation in 2 levels above and 1 below the fractured level with screws in the fractured vertebrae had the greatest maintenance of spine curvature and the lowest implant failure at the final follow-up. There was no difference between the periods of hospital stay (P = 0.788) and blood loss (P = 0.154) among different tiers. The authors concluded that a fixation method consisting of 2 levels above and 1 below with intermediate screws for the thoracolumbar burst fractures showed the highest correction of kyphosis angle both at the immediate and final follow-up with the lowest implant failure. Given that most burst fractures occur at the thoracolumbar junction, this construct choice minimizes the fusion of mobile lumbar segments while providing the highest fracture fixation stability.

Contributed by Dr. Kanwaljeet Garg

Chugh AJS, et al. Stable Spondylolisthesis: Should management change based on presence of facet cysts? Clin Spine Surg 2019. doi: 10.1097/BSD.0000000000000803.

Lumbar facet cysts are common degenerative entities and found in 10-50% of the patients with a low grade (1 or 2) spondylolisthesis. Management of patients with facet cysts is controversial with some authors advocating fusion. The authors aimed to assess if there was any correlation between facet cysts and lumbar instability in this retrospective study involving 86 patients. Preoperative magnetic resonance images were reviewed for the presence of lumbar facet cysts and Facet Fluid Indices (FFI)—calculated as the ratio of facet fluid width to facet width. Instability was defined as a difference of >3 mm in vertebral displacement between flexion and extension radiographs. In total, 26 patients had an unstable and 60 had a stable spondylolisthesis. There was no statistically significant difference in the rate of facet cysts and FFI in patients with unstable and stable spondylolisthesis. FFI in patients with facet cysts was significantly higher than those without (P < 0.05). In addition, the group with facet cysts had a significantly higher proportion of patients with FF effusions >3 mm. The authors concluded that a lack of correlation with instability hints that the presence of facet cysts may not indicate instability in lumbar degenerative spondylolisthesis. Therefore, presence of facet cysts in static magnetic resonance imaging revealing spondylolisthesis should not preclude the physician from performing dynamic films to evaluate for instability.

Contributed by Dr. Kanwaljeet Garg

Wang M, et al. A prediction of postoperative neurological deficits following intracranial aneurysm surgery using somatosensory evoked potential deterioration duration. Neurosurg Rev. 2019. doi: 10.1007/s10143-019-01077-5.

The use of somatosensory evoked potential (SSEP) in intracranial aneurysm surgery is well defined but the relationship between the duration of SSEP deterioration and postoperative neurological deficits (PNDs) is still not clear. This study aimed to detect the relationship between the SSEP deterioration duration and PND; and detect the relationship between SSEP deterioration duration and postoperative computed tomography (CT) findings. Forty patients with SSEP deterioration were enrolled in the study. Four patients had an irreversible disappearance of SSEP intraoperatively, while 36 patients had a reversible deterioration (including 9 patients with reversible reduction and 27 patients with reversible disappearance). The SSEP deterioration duration differed significantly between patients with or without PND (42 ± 46 vs 11 ± 9 min min, P < 0.01). Eleven minutes is the optimal cut-off value of motor evoked potential change duration that avoids a PND from developing. Patients with a SSEP deteriorating duration >11 min had a significant higher incidence rate of abnormal computed tomographic scan finding postoperatively (P < 0.05). The authors concluded that the duration of SSEP deterioration was extremely important in predicting the postoperative neurological function, and in order to avoid PND, the SSEP deterioration duration must not exceed 10 min.

Contributed by Dr. Kanwaljeet Garg

Apra C, et al. Could propranolol be beneficial in adult cerebral cavernous malformations? Neurosurg Rev 2019. doi: 10.1007/s10143-018-01074-0.

Surgery is the most commonly used therapeutic option for cerebral cavernous malformations (CCM) and is proposed, whenever possible, after haemorrhagic events, neurological symptoms, or epilepsy. Radiosurgery, at the moment, remains a controversial alternative in some cases. However, there is no treatment for non-accessible lesions, such as a brainstem CCM, multiple CCMs, or those located in functional areas. Propranolol, a non-selective beta-blocker used as first-line treatment for infantile haemangiomas, has proven to be spectacularly effective in a few cases of adult patients with CCM. There are only a few case reports in the literature describing the use of propranolol for intracranial cavernomas. In the reported patients, propranolol has shown beneficial effects in reducing the number of lesions, their volume, and the onset of haemorrhage, even in long-lasting lesions. The dose and duration of treatment and follow-up was different in all the reported cases, ranging from 6 months in infants to several years. Although propranolol was stopped without complications in one patient, its discontinuation caused rapid deterioration in another. However, further prospective trials are necessary.

Contributed by Dr. Kanwaljeet Garg

Anderson CS, et al. ENCHANTED Investigators and Coordinators. Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): An international, randomised, open-label, blinded-endpoint, phase 3 trial. Lancet. 2019;393:877-88.

The authors of the ENCHANTED trial address a very important question about the outcome of ischemic stroke in patients with intensive blood pressure (BP) lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischemic stroke. The authors performed an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients, (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more. These patients were recruited and screened at 110 sites in 15 countries. Those who were eligible were randomly assigned within 6 h of stroke onset to receive intensive (the goal of systolic blood pressure 130–140 mm Hg within 1 h) or guideline (the goal of systolic blood pressure <180 mm Hg) BP lowering in 72 h. The primary outcome was functional status at 90 days, as measured by the shift in modified Rankin scale scores. At the end of the study, the mean systolic blood pressure over 24 h was significantly lower in the intensive group and 149.8 mm Hg (12.0) in the guideline group (P < 0.0001). The number of intracranial hemorrhages was 160 in the intensive group and 209 in the guideline group, although the outcome between the two groups at the end of 90 days was not significant. The study could not clear the doubt about the optimal blood pressure in patients who undergo thrombolysis. Further studies are needed to clarify this important issue.

Contributed by Dr. Ravi Yadav

Whone A, et al. Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson's disease. Brain 2019;142:512-25.

This study uses a novel study design by investigating a drug delivery system that used glial cell line-derived neurotrophic factor (GDNF). The neurotrophic factors have been found to play an important neuroprotective role in cell death in Parkinson's disease. The authors investigated the effects of GDNF in Parkinson's disease, using an intermittent intraputamenal convection-enhanced delivery via a skull-mounted transcutaneous port. This method is a novel method to potentially afford putamen-wide therapeutic delivery. This was a single-centre, randomized, double-blind, placebo-controlled trial. In this study, six pilot stage patients (randomization 2:1) and 35 primary stage patients (randomization 1:1) received bilateral intraputamenal infusions of GDNF (120 mg per putamen) or a placebo every 4 weeks for 40 weeks. The primary goal was the percentage change from baseline to week 40 in the OFF state (Unified Parkinson's Disease Rating Scale; UPDRS-III). There was no statistically significant benefit between the two groups at the end of the study. Surprisingly, the 18F-DOPA PET (fluoro-18-L-dihydroxyphenylalanine positron emission tomography) imaging showed a significantly increased overall uptake in the putamen only in the active group, ranging from 25% (left anterior putamen; P = 0.0009) to 100% (both posterior putamina; P = 0.0001). The authors ascribed the lack of a clinical effect seen in this study to either a flaw in the clinical evaluation methodology or some collateral effect of the drug. Hence, they stressed the need for an improvement in the methodology for future studies.

Contributed by Dr. Ravi Yadav

Pase MP, et al. Assessment of plasma total tau level as a predictive biomarker for dementia and related endophenotypes. JAMA Neurol. 2019 doi: 10.1001/jamaneurol.2018.4666.

The field of biomarker discovery has led to an explosion of knowledge in the area of dementia. It is seeing new dawn with the advent of newer methods of estimation of the biomarkers. This study declares the result of the use of plasma total tau as a blood biomarker for dementia and related endophenotypes. The authors utilized data from the US community-based Framingham Heart Study with replication in the Memento study, a multicenter cohort of persons with mild cognitive impairment or subjective cognitive complaints, recruited from memory clinics across France. They estimated plasma total tau level using single molecule array technology. In both the Framingham study sample of 1453 cases and the replication sample of 367 patients, the total plasma tau levels correlated with poor cognition and Alzheimer's disease. The findings show that the plasma total tau value could be a useful marker to predict dementia.

Contributed by Dr. Ravi Yadav

Fralick M, et al. Association of concussion with the risk of suicide: A systematic review and meta-analysis. JAMA Neurol 2018 doi: 10.1001/jamaneurol.2018.3487.

This interesting meta-analysis establishes the risk of suicide among the survivors of mild traumatic brain injury and concussion. The analysis shortlisted data from 10 cohort studies, 5 cross-sectional studies, and 2 case-control studies with a large number of patients. The analysis showed a 2-fold higher risk of suicide in patients experiencing concussion and/or mild traumatic brain injury (TBI; relative risk, 2.03 [95%CI,1.47-2.80], P < 0.001). The approximate follow up in this study was 4 years. These survivors were also at a greater risk of suicidal ideation and suicide attempts. The authors lay stress on the need for planning and identifying strategies to tackle this risk factor in the future.

Contributed by Dr. Ravi Yadav

Koch G, et al. Effect of cerebellar stimulation on gait and balance recovery in patients With hemiparetic stroke: A randomized clinical trial. JAMA Neurol 2018 doi: 10.1001/jamaneurol.2018.3639.

Gait and balance impairment are important predictors of recovery in patients with hemiparetic stroke. This study investigates whether intermittent theta (θ) burst stimulation (CRB-iTBS; cerebellar intermittent θ-burst stimulation) of the cerebellum can improve balance and gait functions in these patients. This was a randomized, double-blind, sham-controlled phase IIa trial. The treatment was given for 3 weeks along with physiotherapy. The patients were randomly assigned to sham group or the active stimulation group just before they received physiotherapy. At the end of the study, the active stimulation group had a significantly less step width and better posterior parietal neural activity. The results show that cerebellar theta burst stimulation could improve the gait and balance recovery after hemiparetic stroke with physiotherapy.

Contributed by Dr. Ravi Yadav

Tandon N, et al. Analysis of morbidity and outcomes associated with use of subdural grids vs stereoelectroencephalography in patients with intractable epilepsy. JAMA Neurol. 2019 doi: 10.1001/jamaneurol.2019.0098.

The advent of robotic stereoelectroencephalography (SEEG) for seizure localization has been a revolutionary advancement in the area of surgery for intractable epilepsy. However, there is a lack of adequate data on whether it is actually better than the traditional grid electrodes. This study has attempted to address this question. 260 procedures were performed in 239 patients. In this single center study, subdural grid electrodes (SDE) were implanted using standard techniques while SEEG was placed using a stereotactic robot. Subsequently, surgical resection or laser ablation of the seizure focus was performed. Interestingly, the patients who underwent SEEG had better adverse effect profiles. There were seven symptomatic haemorrhagic sequelae (1 with the permanent neurological deficit), and 3 infections in the SDE cohort with no significant complications in the SEEG cohort (P = .003). Thus, SEEG may have a better adverse adverse effect profile over the conventional SDE in seizure localization.

Contributed by Dr. Ravi Yadav

Nussbaum ES, et al. Microsurgical treatment of unruptured middle cerebral artery aneurysms: a large, contemporary experience. J Neurosurg 2019;130:1498-504.

The authors studied 716 patients with a total of 750 unruptured MCA aneurysms from 1997 to 2015. All surgical procedures, including clipping, wrapping, bypass, and parent artery occlusion, were performed by a single neurosurgeon. Aneurysm occlusion was assessed using intraoperative digital subtraction angiography (DSA) or DSA and indocyanine green video angiography in all cases. Postoperatively, all patients were monitored in a neuro intensive care unit overnight. Clinical follow-up was scheduled for 2–4 weeks after surgery, and angiographic follow-up was performed in those patients with subtotally occluded aneurysms at 1, 2, and 5 years post operation. 649 (86.5%) aneurysms were small, 75 (10.0%) were large, and 26 (3.5%) were giant. Most aneurysms (n = 677, 90%) were treated by primary clip reconstruction. The surgical morbidity rate was 2.8%, and the mortality rate was 0%. Complete angiographic aneurysm occlusion was achieved in 92.0% of aneurysms. At final follow-up, 713 patients had a modified Rankin Scale (mRS) score of 0, 2 patients had an mRS score of 2 or 3, and 1 had an mRS score of 4. The authors concluded that micro neurosurgery for MCA aneurysms can be performed at a high volume centre with a low morbidity.

Contributed by Dr. Anant Mehrotra

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

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

Contributed by Dr. Anant Mehrotra

Lagman C, et al. The meningioma vascularity index: A volumetric analysis of flow voids to predict intraoperative blood loss in nonembolised meningiomas. J Neurosurg 2019; 130:1547-52.

The authors performed a volumetric analyses of 51 intracranial meningiomas (21 preoperatively embolized) resected at their institution. Through the use of image segmentation software and a voxel-based segmentation method, flow void volumes were measured on T2-weighted MR images. This metric was named the Meningioma Vascularity Index (MVI). The primary outcomes were intraoperative estimated blood loss (EBL) and perioperative blood transfusion. In the non-embolized group, the MVI correlated with intraoperative EBL when controlling for tumor volume (r = 0.55, P = 0.002). The MVI also correlated with the perioperative blood transfusion (P = 0.001). A greater MVI was associated with an increased risk of blood transfusion (odds ratio [OR] 5.79, 95% confidence interval [CI] 1.15–29.15) and subtotal resection (OR 7.64, 95% CI 1.74–33.58). In the embolized group, those relationships were not found. There were no significant differences in MVI, intraoperative EBL, or blood transfusion across the groups.

Contributed by Dr. Anant Mehrotra

Meybodi AT, et al. The pterygoclival ligament: A novel landmark for localization of the internal carotid artery during the endoscopic endonasal approach. J Neurosurg 2019;130:1699-709.

The authors of this interesting paper prepared ten cadaveric heads for transnasal endoscopic dissection. The floor of the sphenoid sinus was drilled to expose an extension of the pharyngobasilar fascia between the sphenoid floor and the pterygoid process (the pterygoclival ligament). Several features of the pterygoclival ligament were assessed. In addition, 31 dry skulls were studied to assess the features of the bony groove harboring the pterygoclival ligament. The pterygoclival ligament was identified bilaterally during drilling of the sphenoid floor in all specimens. The ligament started a few millimeters posterior to the posterior end of the vomer alae and invariably extended posterolaterally and superiorly to blend into the fibrous tissue around the lacerum ICA. The mean length of the ligament was 10.5 ± 1.7 mm. The mean distance between the anterior end of the ligament and the midline was 5.2 ± 1.2 mm. The mean distance between the posterior end of the ligament and the midline was 12.3 ± 1.4 mm. The bony pterygoclival groove was identified at the confluence of the vomer, pterygoid process of the sphenoid, and basilar part of the occipital bone, running from the posterolateral to the anteromedial aspect. The mean length of the groove was 7.7 ± 1.8 mm. Its posterolateral end faced the anteromedial aspect of the foramen lacerum medial to the posterior end of the vidian canal. A clinical case illustration is also provided by the authors.

Contributed by Dr. Anant Mehrotra

Tan K, et al. Diffusion tensor imaging and ventricle volume quantification in patients with chronic shunt-treated hydrocephalus: A matched case-control study. J Neurosurg 2018. DOI: 10.3171/2017.6.JNS162784.

The authors conducted a study on 21 patients of hydrocephalus who had been treated with shunt placement before 2 years of age and these were compared with age and sex matched healthy controls. The authors conducted DTI imaging on a 3T MRI scanner. Outcome was scored based on the Headache Disability Inventory and the Hydrocephalus Outcome Questionnaire. Fractional anisotropy (FA) and other DTI-based measures (axial, radial, and mean diffusivity; AD, RD, and MD, respectively) were extracted in the corpus callosum and internal capsule with manual region-of-interest delineation; and, in other regions with tract-based spatial statistics (TBSS). The authors found significantly lower FA for patients than for controls in 20 of the 48 regions, mostly posterior white matter structures, in the periventricular as well as more distal tracts. Of these 20 regions, 17 demonstrated increased RD, while only 5 showed increased MD and 3 showed decreased AD. No areas of increased FA were observed. The authors concluded that TBSS-based DTI is a sensitive technique for elucidating changes in white matter structures due to hydrocephalus and chronic cerebrospinal fluid shunting.

Contributed by Dr. Anant Mehrotra

Goyal A, et al. Clinical presentation, natural history and outcomes of intramedullary spinal cord cavernous malformations J Neurol Neurosurg Psychiatry 2019;90:695-703.

Spinal intramedullary cavernomas sometimes pose a management dilemma. Contemplating surgery in a patient with a sizeable cavernoma in the spinal cord who is otherwise minimally symptomatic is a tough decision to make. In this regard, this article assumes importance for the neurosurgical community. A total of 107 patients were studied by the authors. They defined haemorrhage was defined as clinical worsening in tandem with imaging changes visualised on follow-up MRI. The outcomes assessed included neurological status and annual haemorrhage rates. While 21 (24.7%) patients underwent immediate surgical resection, 64 (75.3%) were initially managed conservatively. In the latter group, 16 (25.0%) suffered a haemorrhage during follow-up and 11 (17.2%) required surgical resection due to interval bleeding or neurological worsening. The overall annual risk of haemorrhage was 5.5% per person year. The rate among patients who were symptomatic and asymptomatic on presentation was 9.5% and 0.8%, respectively, with the median time to haemorrhage being 2.3 years (0.1–12.3). Univariate analysis identified a higher lesion size (P = 0.024), the history of prior haemorrhage (P = 0.013) and the presence of symptoms (P = 0.003) as risk factors for a subsequent haemorrhage. Multivariable proportional hazards analysis revealed the presence of symptoms to be independently associated with haemorrhage during follow-up (HR 9.39, CI 1.86 to 170.8, P = 0.013). Thus, large, symptomatic intramedullary cavernomas may represent a special risk group where surgery may be considered.

Contributed by Dr Kuntal K. Das

Ferraro S, et al. Interhemispherical anatomical disconnection in disorders of consciousness patients. J Neurotrauma 2019;36:1535-43.

In patients with disorders of consciousness (DOC), the corpus callosum (CC) and subcortical white matter (SWM) integrity tend to discriminate between the diagnostic categories. The authors intended to study the link between the integrity of CC and of SWM and the clinical status in DOC patients, disentangling the role played by the different brain injuries (traumatic or hemorrhagic brain injury) and also to investigate the relationship between the CC integrity and the brain metabolism. They assessed the diagnostic accuracy of the CC and SWM integrity, using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (sMRI), in a sample of individuals with DOC, well balanced for the diagnosis and etiology. The CC DTI-derived measures were correlated with the brain metabolism, computed with fluorodeoxyglucose positron emission tomography. Their results showed that the CC macrostructural DTI-derived measures could indeed discriminate between the two diagnosis and correlate with the clinical status of DOC patients irrespective of the etiology. Moreover, the CC DTI-derived measures strongly correlated with the metabolism of the right hemisphere. They concluded that the degree of the interhemispherical anatomical disconnection was a marker of the level of consciousness independent from the type of brain injury. They also concluded that the observed CC alterations might be the consequence of the reduced brain metabolism. Remarkably, the results of this study suggest that the functional interplay between the two hemispheres is linked tightly to the level of consciousness.

Contributed by Dr Kuntal K. Das

Boire A, et al. Liquid biopsy in central nervous system metastases: A RANO review and proposals for clinical applications Neuro Oncol. 2019;21:571-84.

Liquid biopsies represent an exciting new prospect in the field of neuro-oncology. Essentially, it includes collection and analysis of various components of a tumor that find their way into the circulation. These tumor components are often regarded as surrogates for tumor tissue in the management of both primary and secondary brain tumors. In this interesting review article, Boire A et al., provide a comprehensive and critical review of the literature on the various liquid biopsy targets like spinal fluid and blood circulating tumor cells (CTCs) cell free tumor (ctDNA) in the diagnosis and management of parenchymal brain metastasis with or without leptomeningeal dissemination. This article also provides an in depth discussion on the various technical issues and several potential applications in different clinical setting. The review also provides a glimpse of the currently ongoing clinical studies on liquid biopsies for brain metastasis and lays out certain recommendations for their clinical usage in the future.

Contributed by Dr Kuntal K. Das

Sneiders D, et al. Outcomes of single versus double fascicular nerve transfers for restoration of elbow flexion in patients with brachial plexus injuries: A systematic review and meta-analysis Plast Reconstr Surg. 2019 doi: 10.1097/PRS.0000000000005720.

Brachial plexus injuries are devastating injuries. Of late, surgical reconstruction seems to be emerging as a hope to the victims, almost all of whom are adults in the prime of their lives. Restoration of elbow function is one of the top priorities in brachial plexus repair. Elbow flexion after upper brachial plexus injury may be restored by a nerve transfer from the ulnar nerve to the biceps motor branch with an optional nerve transfer from the median nerve to the brachialis motor branch (single and double fascicular nerve transfer). This meta-analysis assesses the effectiveness of both techniques and the added value of additional reinnervation of the brachialis muscle. Comprehensive searches were performed identifying studies concerning restoration of elbow flexion through single and double fascicular nerve transfers. Only C5-C6 lesion patients were included in the quantitative analysis to prevent confounding by indication. Primary outcome was the proportion of patients reaching British Medical Research Council (BMRC) elbow flexion grade ≥3. The meta-analysis was performed with random effect models (REM). A total of 35 studies were included (n = 688) out of which 29 studies reporting quantitative analysis (n = 341) were included. After the single fascicular nerve transfer, 190/207 patients (REM: 95.6%; 95%CI: 92.9-98.2), and after the double fascicular nerve transfer, 128/134 patients reached MRC ≥3 (REM: 97.5%; 95%CI: 95.0-100) (P = 0.301). Significantly more double nerve transfer patients reached MRC ≥4 if the pre-operative delay was ≤6 months (84/101 vs. 49/51; P = 0.035). Additional reinnervation of the brachialis muscle did not result in significantly more patients reaching MRC ≥3 elbow flexion. Double fascicular nerve transfer may result in more patients reaching MRC ≥4 in patients with a pre-operative delay under 6 months. The median nerve may be preserved or used for another nerve transfer without substantially impairing elbow flexion restoration.

Contributed by Dr Kuntal K. Das






 

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