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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 6  |  Page : 1378-1390

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

1 Department of Neurosurgery, Global Hospitals and Health City, Chennai, Tamil Nadu, India
2 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
3 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
4 Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
5 Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
6 Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
7 Department of Radiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication10-Nov-2017

Correspondence Address:
Dr. K Sridhar
Department of Neurosurgery, Institute of Neurological Sciences and Spinal Disorders, Global Hospitals and Health City, 439, Cheran Nagar, Perumbakkam, Chennai - 600 100, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.217991

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How to cite this article:
Sridhar K, Turel MK, Tripathi M, Yadav R, Takkar A, Mehta S, Das KK, Mehrotra A, Ahuja CK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India 2017;65:1378-90

How to cite this URL:
Sridhar K, Turel MK, Tripathi M, Yadav R, Takkar A, Mehta S, Das KK, Mehrotra A, Ahuja CK. A summary of some of the recently published, seminal papers in neuroscience. Neurol India [serial online] 2017 [cited 2023 Feb 4];65:1378-90. Available from: https://www.neurologyindia.com/text.asp?2017/65/6/1378/217991

Goes R, et al. Risk of aspirin continuation in spinal surgery: A systematic review and meta-analysis. Spine J pii: S1529-9430 (17) 30912-9. doi: 10.1016/j.spinee. 2017.08.238.

Aspirin is usually discontinued prior to performance of surgery due to the risk of hemorrhagic complications. The authors conducted a metaanalysis to evaluate all available evidence about continuation of aspirin and to compare the peri- and post-operative blood loss and complication rates between patients who continued aspirin and those who discontinued aspirin peri-operatively in spinal surgery. No significant differences in the mean operating time and the mean peri-operative blood loss were seen between the aspirin-continuing group and the aspirin-discontinuing one. Similar non-significant differences between the two groups were found for cardiac events, stroke, and surgical site infections. This meta-analysis showed an absence of significant differences in peri-operative complications between aspirin continuation and discontinuation. Due to the paucity of included studies, further well-designed prospective trials are imperative to demonstrate the potential benefit and safety of continuation of aspirin therapy prior to surgery.

Contributed by Dr. Mazda K. Turel

Nagoshi N, et al. Risk Factors for and clinical outcomes of dysphagia after anterior cervical surgery for degenerative cervical myelopathy: Results from the AOSpine International and North America Studies. J Bone Joint Surg Am 2017;99:1069-77.

The aim of this study was to determine the prevalence of and the risk factors for dysphagia, and the impact of this complication on short and long-term clinical outcomes, in patients treated with anterior cervical decompression and fusion. Four hundred and seventy patients undergoing a 1-stage anterior or 2-stage anteroposterior cervical decompression and fusion were enrolled in the prospective AO Spine CSM (Cervical Spondylotic Myelopathy) North America or International study at 26 global sites. The overall prevalence of dysphagia was 6.2%. The most important predictors of dysphagia were detected to be the presence of an endocrine disorder, greater number of decompressed levels, and 2-stage surgery. At the time of both short and long-term follow-up, patients with perioperative dysphagia exhibited improvement in functional disability and quality-of life scores that were similar to those of patients without dysphagia.

Contributed by Dr. Mazda K. Turel

Kubota G, et al. Platelet-rich plasma enhances bone union in posterolateral lumbar fusion: A prospective randomized controlled trial. Spine J 2017. pii:S1529-9430 (17) 30488-6. doi: 10.1016/j.spinee. 2017.07.167.

The objective of this study was to evaluate the efficacy of platelet-rich plasma (PRP) after posterolateral lumbar fusion (PLF) surgery. The authors randomized 62 patients who underwent one- or two-level instrumented PLF for lumbar degenerative spondylosis with instability, to either the platelet-rich plasma (PRP; 31 patients) or the control (31 patients) groups. Data from 50 patients with complete data were included. The bone union rate at the final follow-up was significantly higher in the PRP group (94%) than in the control group (74%). The area of fusion mass was significantly higher in the PRP group (572 mm2 ) than in the control group (367 mm2 ). The mean period necessary for union was 7.8 months in the PRP group and 9.8 months in the control group. In the PRP group, the platelet count was 7.7 times higher and the growth factor concentrations were 50 times higher than those found in plasma. However, there was no significant difference in low back pain, leg pain, and leg numbness in either of the groups at any time when the evaluation was performed. The authors concluded that patients treated with PRP showed a higher fusion rate, greater fusion mass, and more rapid bony union after spinal fusion surgery than patients not treated with PRP.

Contributed by Dr. Mazda K. Turel

Donk RD, et al. What's the best surgical treatment for patients with cervical radiculopathy due to single-level degenerative disease? A randomized controlled trial. PLoS One 2017;12:e0183603

An attempt was made to investigate the efficacy of adding supplemental fusion or arthroplasty to cervical anterior discectomy for symptomatic mono-level cervical degenerative disease (radiculopathy). A randomized controlled trial was reported with a 9- year follow up comparing anterior cervical discectomy without fusion with fusion by cage stand alone, or with disc prosthesis, in patients with cervical radiculopathy due to a single-level cervical disc degeneration.

142 patients between 18 and 55 years were randomly allocated to one of the groups. Neck disability index at the last follow-up did not differ between the three treatment groups, nor did the secondary outcomes such as the MacGill Pain Questionnaire Dutch Language Version (MPQ-DLV), as well as the physical-component summary (PCS) and the mental class summary (MCS) of the 36-item Short-Form health form (SF-36). The major improvement occurred within the first 6 weeks after surgery. After that, the changes remained stable. Eleven patients underwent surgery for recurrent symptoms and signs due to nerve root compression at the index or adjacent level. No difference could be detected between the three surgical modalities for treating a single-level degenerative disc disease. In the presence of radiculopathy due to a single level disc prolapse, the results of an anterior cervical discectomy without implant seems to be similar to anterior cervical discectomy with fusion by a stand-alone cage or by using a disk prosthesis. However, more confirmatory results would be expected with a larger cohort size.

Contributed by Dr. Mazda K. Turel

Kato S, et al. Does surgical intervention or timing of surgery have an effect on neurological recovery in the setting of a thoracolumbar burst fracture? J Orthop Trauma 2017;31 Suppl 4:S38-S43.

Traumatic thoracolumbar burst fractures are one of the most common forms of spinal trauma with the majority occurring at the junctional area where mechanical load is maximal (AO Spine Thoracolumbar Spine Injury Classification System Subtype A3 or A4). Recent evidence has revealed that long term functional outcomes may be equivalent between the operative and non-operative management for neurologically intact patients with thoracolumbar burst fractures. Nevertheless, consensus has not been established regarding the optimal treatment strategy for those patients with neurological deficits. Although operative management is generally recommended for thoracolumbar fractures with significant neurological deficits, the evidence is weak, and nonoperative management can also be an option for those with solitary radicular symptoms. With regards to the timing of operative management, high-quality studies comparing early and delayed intervention are lacking. This review article reveals that as is true in cervical spine injury, an early intervention would also be beneficial and ensure an early neurological recovery in patients with a thoracolumbar burst fracture but more studies with a larger number of patients and follow up are required to answer these questions.

Contributed by Dr. Mazda K. Turel

van den Bent MJ, et al. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: A phase 3, randomised, open-label intergroup study. Lancet 2017. pii: S0140-6736(17) 31442-3.

The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q co-deleted tumours, has not yet been established. In this study, the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas was evaluated.

This was a phase 3, randomised, open-label study. Patients were assigned in equal numbers (1:1:1:1) Group 1 received radiotherapy (59.4 Gy in 33 fractions of 1.8 Gy) alone; Group 2 received radiotherapy with adjuvant temozolomide (12 4-week cycles of 150-200 mg/m2 with temozolomide being given on days 1-5); Group 3 received radiotherapy with concurrent temozolomide 75 mg/m2 per day, with adjuvant temozolomide; and, Group 4 received received radiotherapy with concurrent temozolomide 75 mg/m2 per day, without adjuvant temozolomide. At the time of the interim analysis, 745 (99%) of the planned 748 patients had been enrolled. The overall survival at 5 years was 56% with and 44% without adjuvant temozolomide. The authors concluded that adjuvant temozolomide chemotherapy was associated with a significant survival benefit in patients with newly diagnosed non-co-deleted anaplastic glioma.

Contributed by Dr. Mazda K. Turel

Wernicke AG, et al. Clinical outcomes of large brain metastases treated with neurosurgical resection and intraoperative Cesium-131 brachytherapy: Results of a prospective trial. Int J Radiat Oncol Biol Phys. 2017;98:1059-68

When adjuvant stereotactic radiosurgery is given to the cavity of resected brain metastases, larger tumors (>2 cm) have greater rates of recurrence and radionecrosis (RN). The present study assessed the effects of low-dose 131Cesium brachytherapy on the local control and RN in patients treated for large brain metastases in 42 patients with 46 metastases. The patients underwent surgical resection with intraoperative placement of stranded 131Cs seeds. The local freedom from progression (FFP), the regional and distant FFP, overall survival (OS), and RN rate were assessed. Failures 5 to 20 mm from the tumor cavity and dural-based failures were considered as regional recurrences.

The median follow-up period was 12 months. The metastases had a median preoperative diameter of 3 cm (range 2.0-6.8cm). The local progression-free rate was 100% for all tumor sizes. Regional recurrence developed in 7% of the patients. Distant recurrences were found in 41% of the patients. The median OS was 15 months, with a 1-year OS rate of 58%. The lesion size was not significantly associated with any survival endpoint on univariate or multivariate analysis. The authors concluded that intraoperative 131Cs brachytherapy is a promising and effective therapy for large brain metastases requiring neurosurgical intervention as it can offer improved local control and lesser RN within the resection cavity, when compared with stereotactic radiosurgery.

Contributed by Dr. Mazda K. Turel

Hassan H, et al. Survival rates and prognostic predictors of high grade brain stem gliomas in childhood: A systematic review and meta-analysis. J Neurooncol 2017. doi: 10.1007/s11060-017-2546-1.

This systematic review and meta-analysis was undertaken to determine the survival rates and assess the potential prognostic factors including the selected interventions. The studies included in the study involved pediatric participants with high grade brain stem gliomas diagnosed by magnetic resonance imaging or biopsy. It reported the overall survival rates of the patients. Sixty-five studies (2336 participants) were included. The meta-analysis showed an one - year overall survival (OS) of 41%, a 2-year OS of 15% and a 3-year OS of 7%. The subgroup analysis comparing the date of study, classification of tumor, use of temozolomide, non-standard interventions or phase 1/2 versus other studies demonstrated no difference in survival outcomes. The authors concluded that survival outcomes of high grade brain stem gliomas have remained very poor, and do not clearly vary according to classification, phase of study or the use of different therapeutic interventions.

Contributed by Dr. Mazda K. Turel

Marinoff AE, et al. Rethinking childhood ependymoma: A retrospective, multi- center analysis reveals poor long-term overall survival. J Neurooncol 2017. doi: 10.1007/s11060-017-2568-8.

The authors conducted a review of 463 pediatric patients with a World Health Organisation Grades II/III intracranial ependymoma. The median follow-up time was 11 years. The ten-year overall survival (OS) and progression free survival (PFS) were 50% and 29%, respectively. Gross total resection (GTR) and grade II pathology were associated with significantly improved OS. However, GTR was not curative in all children. The ten-year OS for patients treated with a GTR was 61%, and the PFS was 36%. Pathological examination confirmed most recurrent tumors to be ependymoma, and 74% of the tumors occurred at the primary tumor site. Current treatment paradigms are not sufficient to provide long-term cure for children with ependymoma. The findings highlight the urgent need to develop novel treatment approaches for this devastating disease.

Contributed by Dr. Mazda K. Turel

Leal-Noval SR, et al. Red blood cell transfusion guided by near infrared spectroscopy in neurocritically ill patients with moderate or severe anemia: A randomized, controlled trial. J Neurotrauma 2017;34:2553-59.

In neurocritically ill patients (NCPs), the use of hemoglobin level as the sole indicator for red blood cell transfusion (RBCT) can result in under- or over-transfusion. This randomized controlled trial was conducted to ascertain if transcranial oxygen saturation (rSO2 ) threshold, as measured by near-infrared spectroscopy, reduces RBCT requirements in anemic NCPs (those patients suffering from closed traumatic brain injury or subarachnoid/intracerebral hemorrhage), compared with hemoglobin threshold alone. Patients with a hemoglobin level of 70-100 g/L received RBCTs to attain an rSO2 >60% (the rSO2 arm) or to maintain hemoglobin between 85 and 100 g/L (the hemoglobin arm). A total of 102 NCPs (51 in each group) were included in the intention-to-treat analysis. Compared with those from the hemoglobin arm, patients in rSO2 arm received fewer RBC units (1 vs. 1.5 units/patient; p < 0.05) and showed lower hemoglobin levels while in protocol. There were no differences between the study arms regarding the percentage of transfused patients (59% vs. 71%), stay in the neurocritical care unit (21 vs. 20 days), unfavorable Glasgow Outcome Scale scores at hospital discharge (57% vs. 71%), in-hospital mortality (6% vs. 10%), or 1 year mortality (24% vs. 24%). Among NCPs with hemoglobin concentrations of 70-85 g/L, withholding transfusion until rSO2 is < 60% may result in reduced RBC requirement compared with routinely transfusing blood to attain a hemoglobin level > 85 g/L. Further studies are required to confirm this finding and its possible impact on clinically significant outcomes.

Contributed by Dr. Mazda K. Turel

Ren Y, et al. Efficacy of closed continuous lumbar drainage on the treatment of postcraniotomy meningitis: A retrospective analysis of 1062 cases. World Neurosurg 2017. 106:925-931. doi: 10.1016/j.wneu. 2017.07.073.

This study aimed at evaluating the efficacy of closed continuous lumbar drainage (CCLD) in the treatment of postcraniotomy meningitis. A total of 1062 adult patients with postcraniotomy meningitis were included. Of these, 474 received intravenous antibiotic therapy, steroid administration and adjuvant CCLD (experimental Group). The remaining 588 patients only received intravenous antibiotic and steroid therapy (control group). In the experimental group, meningitis-related mortality was 2.7%, and 77.4% individuals achieved a Glasgow Outcome Scale of 4-5. In the control group, meningitis-related mortality reached 11.6%, with only 61.1% of patients achieving a GOS of 4-5. The time-to-negative cerebrospinal fluid laboratory test and the duration of meningitis-related symptoms were significantly shorter in the experimental group as compared with the control group. Thus, intravenous antibiotic and steroid therapies combined with CCLD appear to be effective and safe treatment for postcraniotomy meningitis.

Contributed by Dr. Mazda K. Turel

Arnone GD, et al. Surgery for cerebellar hemorrhage - a national surgical quality database improvement program database analysis of patient outcomes and factors associated with 30 day mortality and prolonged ventilation. World Neurosurg 2017. 106:543-550. doi: 10.1016/j.wneu. 2017.07.041.

Primary cerebellar hemorrhage accounts for 10% of all intracranial hemorrhages. The authors examined outcomes following surgery for primary cerebellar hemorrhage, and identified risk factors associated with adverse outcomes. 158 craniotomies were studied, with a 30-day mortality rate of 27%. The most common adverse events included ventilator dependence after 48 hours (49%) and pneumonia (24%). Almost one quarter (25%) of the patients required additional operations, with 9% of patients undergoing a repeat craniotomy. The authors concluded that the presence of cerebellar hemorrhage is associated with an significant risk of mortality and ventilator dependence. In patients who require surgery, the 30-day mortality risk remains high (26.6%), with the functional status and the American Society of Anesthesiologists class being predictive of death.

Contributed by Dr. Mazda K. Turel

Gorelick PB, et al.; American Heart Association/American Stroke Association. Defining optimal brain health in adults: A presidential advisory from the American Heart Association/American Stroke Association. Stroke 2017;48:e284-e303.

Cognitive function may often be compromised in an aging person and predicts the patient's quality of life, functional independence, and the risk of institutionalization. The purpose of this advisory was to provide an initial definition of optimal brain health in adults. Seven metrics were used to define optimal brain health in adults: 4 ideal health behaviours (nonsmoking, physical activity at goal levels, a healthy diet consistent with the current guideline levels, and body mass index <25 kg/m2 ); and 3 ideal health factors (untreated blood pressure < 120/<80 mm Hg, untreated total cholesterol <200 mg/dL, and fasting blood glucose <100 mg/dL). In addition, control of cardiovascular risk factors as well as a healthy social engagement have also been included to define optimal health in adults.

Contributed by Dr. Mazda K. Turel

Tian KB, et al. Clinical course of untreated thalamic cavernous malformations: Hemorrhage risk and neurological outcomes. J Neurosurg 2017;127:480-491.

The authors undertook this study to obtain the prospective hemorrhage rate and to provide a better understanding of the prognosis of 121 untreated thalamic cavernous malformations (CMs) with a mean follow-up duration of 3.6 years. The overall annual hemorrhage rate (subsequent to the initial presentation) was calculated to be 9.7%. This rate was highest in patients who initially presented with hemorrhage and focal neurological deficits (FNDs), followed by patients with hemorrhage but without FND, and patients without hemorrhage regardless of symptoms. The initial patient presentation of hemorrhage with FND and an associated developmental venous anomaly (DVA) were identified as independent risk factors for haemorrhage. The lesion size and mRS score at diagnosis were independent adverse risk factors for a poor neurological outcome (mRS score ≥2). These findings and the mode of initial presentation are useful for clinicians and patients when selecting an appropriate treatment, although the tertiary referral bias of the series should be taken into account.

Contributed by Dr. Mazda K. Turel

Juvela S, et al. Intracranial aneurysm parameters for predicting a future subarachnoid hemorrhage: A long-term follow-up study. Neurosurgery 2017;81:432-40.

A total of 142 patients with unruptured intracranial aneurysms (UIAs) diagnosed between 1956 and 1978 were followed prospectively until the patients developed a subarachnoid haemorrhage (SAH) or died, or until the last contact with them. During a follow-up of 3064 person-years, 34 patients suffered from an aneurysm rupture. In the multivariable analyses, the aneurysm volume, volume-to-ostium area ratio, and the bottleneck factor separately as continuous variables predicted aneurysmal rupture. All morphological indices were higher after the rupture than before. In the final multivariable analyses, current status of the patient's smoking, age, and UIA diameter ≥7 mm at baseline were independent risk factors for a future rupture. The aneurysm growth during the follow-up assessment was associated with smoking and SAH. The authors concluded that of the morphological indices, UIA volume seems to most optimally predict a future rupture. Retrospective evaluation of aneurysmal indices that are measured after its rupture are of little value in risk prediction.

Contributed by Dr. Mazda K. Turel

Katsoulakis E, et al. A detailed dosimetric analysis of spinal cord tolerance in high-dose spine radiosurgery. Int J Radiation Oncol Biol Phys 2017;99:598-607.

One of the greatest criticisms against single fraction high dose spinal radiosurgery is the undefined radiobiology of the spine. For intracranial lesions, the tolerance limits for various intracranial structures have already been validated and defined but the same is not true for spinal pathologies in different columns and compartments. The high conformity and dosimetry afforded by various radiosurgery tools, such as the cyber knife, is rapidly replacing conventional radiotherapy, especially for radioresistant tumors such as renal cell carcinoma and melanoma. Anecdotal case reports mention the occurrence of radiation induced myelitis; the total number of patients treated with radiosurgery, however, cannot be ascertained from these single reports to assess the actual incidence of radiation induced complications. In this prospective pooled analysis of 228 patients treated over a 7-year duration, a dose volume histogram (DVH) analysis was performed to evaluate the incidence of radiation induced myelitis in the absence of tumor progression. Though this study failed to define any specific dose volume thresholds or relationships attributable to myelitis, it concluded that the maximum delivered radiation dosage of 13.85 Gy is safe and carries a low risk of myelitis in the range of < 1%. This study is unique as it reports on this morbid complication with a systematic follow up and DVH calculation. One limitation of the study is the exclusion of intramedullary lesions from the analysis.

Contributed by Dr. Manjul Tripathi

Goldbrunner R, et al. EANO guidelines for the diagnosis and treatment of meningiomas. Lancet Oncol 2016;17:e383-e391.

In the absence of any class one treatment guideline, management of intracranial meningiomas is based on personal preference, institutional protocols, and whether or not, there is availability of alternate treatment modalities such as radiosurgery. However, there are several situations which demand special mention such as surgical intervention for a meningioma with unknown growth kinetics; or, the role of adjuvant treatment options for residual grade I meningiomas. Apart from a regular histopathological analysis, a molecular classification is a must and will be the predictive parameter for management decisions. This evidence based guideline has been framed utilizing the World Health Organisation (WHO) 2016 classification with inclusion of molecular targets, thus providing an individualized approach for every meningioma. A primary and residual grade 1 meningioma of similar volume definitely deserves a

different approach. A residual meningioma should be considered as a tumor with a recurrent propensity to grow due to the fact that its growth kinetics had earlier resulted in a size demanding surgical excision. There are no conclusive remarks about the role of adjuvant chemotherapy but the initial studies targeting peptide receptor nucleotide therapy have shown promising results. For a small volume grade II meningioma, stereotactic radiosurgery and conventional radiotherapy give similar tumor control but for large residual lesions, radiotherapy should be preferred. Anti-angiogenic pharmacotherapy should only be considered to presevent further progression of grade II meningioma. Management options for WHO grade III meningiomas are poorly defined because of the smaller number of cases encountered and the very high risk of neurofibromatosis 2 mutations existing in such cases. They should receive adjuvant radiotherapy but there is no consensus on the role of chemotherapy in such cases.

Contributed by Dr. Manjul Tripathi

Storrs C. How poverty affects the brain. Nature. 2017;547:150-2.

This interesting and intriguing study tries to ascertain the role of the fundamental evil of economic science, poverty, and its role in the development of human brain. This is a proven fact that nutrition is the factor which defines the growth and physical development; however, the extent to which nutrition actually affects individuals remains variable. Earlier studies in the 1960s described that protein supplementation in the earlier years of life led to the attainment of a better height and higher intelligence in malnourished children in Guatemala. This study, conducted in Bangladesh, categorically mentions that a poor diet and repeated bouts of diarrhea are the predictors of intellectual deficits and a higher mortality. The highlight of this study was to develop investigative parameters to detect malnutrition early in the disease process by non-invasive monitoring such as functional infrared spectroscopy. The effects of malnutrition are observed over prolonged periods of time (sometimes occurring over a period of up to three decades) and are devastating for the functional and vocational development of the child. It would be interesting to determine whether or not interventions are working as early as is possible, as this would lead to remedial measures that would help in the prevention of these complications. Simple investigative parameters, such as infrared spectroscopy and electroencephalography-detected electrical activity, may identify malnutrition in a timely manner. Easy preventive options such as regular supplementation of banana and chickpeas in the diet may prevent repeated bouts of diarrhea and malnutrition. Such studies should be encouraged as babies do not have the capacity to withstand any insult to their cognitive and other higher mental functions and third world countries do not have the financial backup for costly interventions. We need a middle path of an early detection of malnutrition and its prevention by appropriate interventions to avoid cognitive and developmental effects in children from developing, in order to have a stronger future.

Contributed by Dr. Manjul Tripathi

Zhou G, et al. Association of wall shear stress with intracranial aneurysm rupture: Systematic review and meta-analysis. Sci Rep 2017;13;7:5331.

Management of unnruptured intracranial aneurysms remains a controversial topic and updates in neurosciences keep on adding new clinicoradiological parameters to guide the treatment options. This interesting meta-analysis has attempted to summarise the findings of published literature on the role of wall shear stress (WSS) and its role in aneurysm formation as well as rupture with computational fluid dynamics (CLD) findings. This analysis has shown a significantly higher rate of low WSS associated with aneurysmal rupture and a higher WSS associated with aneurysmal formation. In synchronisation with these clinical findings, posterior circulation aneurysms had a lower WSS than anterior circulation aneurysms. Among the anterior circulation aneurysms, posterior communicating artery aneurysms had a lower WSS than anterior communicating artery and middle cerebral artery aneurysms. Though the findings are interesting, the study fails to provide any conclusive remark regarding the WSS values beyond which one definitely needs to intervene. The threshold for WSS could not be defined but it definitely remains an area of active research as screening programs and frequent radioimaging has led to a higher detection of intracranial aneurysms.

Contributed by Dr. Manjul Tripathi

Sweegers MG, et al. Which exercise prescriptions improve quality of life and physical function in patients with cancer during and following treatment? A systematic review and meta-analysis of randomised controlled trials. Br J Sports Med 2017. pii: bjsports-2017-097891. doi: 10.1136/bjsports-2017-097891.

Many previous randomized control trials (RCTs) and meta-analyses have proven the beneficial effects of exercise during and following cancer therapy on the self-reported quality of life (QOL) and self-reported physical function. However, a few have questioned the role of exercise, the differences in its delivery, as well as the extent and timing of this intervention, in bringing about substantial improvement in the quality of life of patients suffering from cancer. This meta-analysis of 69 RCTs on this topic has summated some important findings. The analysis has determined that a significant improvement in the self-reported QOL and physical function occurs only in the cases where a supervised exercise program has been undertaken and that this benefit is not seen in the unsupervised exercise programs. Irrespective of the cancer type and etiology, there was no significant difference in the effects of intervention based upon variations in the intervention time and duration, or exercise frequency, intensity or the time at which it is performed. The positive effects of the unsupervised exercise intervention on the self-reported physical functions are larger only when they are prescribed at a higher weekly energy expenditure. It can be concluded that regardless of the organ involved by cancer, an exercise regimen in a supervised manner helps in improving the QOL and basic physical function of the patients; hence, it should be included in the regular treatment plan.

Contributed by Dr. Manjul Tripathi

Suwanwela NC, et al.; IVIS study group. A randomized controlled study of intravenous fluid in acute ischemic stroke. Clin Neurol Neurosurg 2017;161:98-103.

This prospective, multicenter, randomized, open label trial was designed to compare the outcome of patients with acute ischemic stroke who received intravenous fluids versus the patients who did not receive intravenous fluids. Blinded patient assessment was done in patients with acute ischemic stroke aged between 18 and 85 years with the National Institutes of Health Stroke Scale (NIHSS) score from 1 to 18 who presented within 72 h after onset of stroke.

Patients were randomly assigned to receive 0.9% NaCl solution, 100 ml/h for 3 days, or no fluids. The interim un-blinded safety analysis suggested significant and early neurological deterioration in the non-intravenous fluid group. Therefore, the study was prematurely discontinued after enrollment of 120 patients.

Predictors of neurological deterioration were a higher NIHSS score, a higher plasma glucose, and an increased pulse rate. The authors concluded that administration of 0.9% NaCl, 100 ml/h for 72 h, in patients with acute ischemic stroke is safe and may be associated with a reduced risk of neurological deterioration. These study findings support the use of intravenous fluid in acute ischemic stroke patients with NIHSS less than 18, who have no existing contraindications to this therapy.

Contributed by Dr. Aastha Takkar

Thormann A, et al. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology 2017; pii: 10.1212/WNL.0000000000004508. doi: 10.1212/WNL.0000000000004508.

Often in multiple sclerosis, the associated non- neurological manifestations take a back seat. In this population based, nationwide cohort study that included all multiple sclerosis (MS) patients in Denmark with their first MS symptom manifesting in the period between 1980 and 2005, the effect of chronic comorbidity at the time of diagnosis, as well as the mortality in MS was investigated.

8,947 individuals with the clinical onset of MS between the said timeline were enrolled. Statistically significant odds ratios for longer diagnostic delays with cerebrovascular, cardiovascular, lung, diabetes, and cancer comorbidity were observed. Similarly, in the mortality study, higher hazard ratios with psychiatric, cerebrovascular, cardiovascular, lung, diabetes, cancer, and Parkinson's disease comorbidity were observed. It was finally concluded that an increased awareness of both the necessity of neurologic evaluation of new neurologic symptoms in persons with preexisting chronic disease; as well as the institution of an optimum treatment to deal with this comorbidity associated with MS is critical to the well-being of the patients.

Contributed by Dr. Aastha Takkar

Little LM, et al. The QuantiFERON-TB gold in-tube assay in neuro- ophthalmology. J Neuroophthalmol 2017;37:242-6.

Although QuantiFERON-TB Gold In-Tube (QFTGIT) testing is regularly used to detect infection with Mycobacterium tuberculosis, its utility in a patient population with a low risk for tuberculosis (TB) has been questioned. In this cohort study, the efficacy of QFT-GIT testing as a method for detection of the presence of the active TB disease in low-risk individuals in a neuro-ophthalmologic setting was analyzed. 99 patients from 2 neuro-ophthalmologic centers were identified. They had undergone the QFT-GIT testing between January 2012 and February 2016. Patients were divided into groups of negative, indeterminate, and positive QFT-GIT results. Records of patients with positive QFT-GIT results were reviewed for development of latent or active TB, as determined by the clinical, bacteriologic, and/or radiographic evidence. 18 out of these 99 patients had positive QFT-GIT tests. Of these 18 cases, 12 had documentation of chest radiographs or computed tomography which showed no evidence for either active TB or pulmonary latent TB infection (LTBI). 4 had chest imaging, which was indicative of possible LTBI. None of these 18 patients had symptoms of active TB and none developed active TB within the follow-up period. It was concluded that routine testing with QFT-GIT in a low-risk cohort did not diagnose active TB infection. Hence, this investigation should not be recommended routinely for individuals having a low risk for the development of TB , as discerned through patient and exposure history, ocular examination, and clinical judgment, especially in neuro-ophthalmology practice.

Contributed by Dr. Aastha Takkar

Furie KL, et al. Effects of pioglitazone on cognitive function in patients with a recent ischemic stroke or TIA: A report from the IRIS trial. J Neurol Neurosurg Psychiatry. pii: jnnp-2017-316361. doi: 10.1136/jnnp-2017-316361.

Presence of cerebrovascular diseases predisposes patients to develop an increased risk for cognitive dysfunction. Modification of vascular risk factors, including overcoming the insulin resistance, could improve post stroke cognitive function. In the Insulin Resistance Intervention after Stroke (IRIS) trial, patients with a recent episode of ischemic stroke or transient ischemic attack (TIA) were randomized to pioglitazone (target 45 mg daily) or a placebo. All patients were insulin resistant based on a Homeostasis Model Assessment-Insulin Resistance score > 3.0. The modified mini-mental score examination [3 MS] score was assessed for analysis of cognitive function during the follow-up period. Patients were tested at baseline and annually for up to a period of 5 years. Of the 3876 patients who participated in the IRIS trial, 3398 who had an evaluation of their 3MS score at baseline and at least once during the follow-up period were finally included in the analysis. The median 3MS score at baseline was 97 (IQR 93-99). The average overall least squared mean 3MS score increased by 0.27 in the pioglitazone group and by 0.29 in the placebo group. It was concluded that among insulin-resistant patients with a recent ischemic stroke or TIA, pioglitazone did not affect cognitive function, as measured by the 3MS, over 5 years.

Contributed by Dr. Aastha Takkar

Rooney JPK, et al. A case-control study of hormonal exposures as etiologic factors for ALS in women: (Euro-MOTOR). Neurology 2017;89:1-8.

The history of hormonal exposures in women, including their reproductive history, breastfeeding history, history of contraceptive use as well as hormonal replacement therapy, and gynecological surgical history, were recorded with a validated questionnaire to investigate the role of hormonal risk factors in the development of amyotrophic lateral sclerosis (ALS) in this case controlled trial. 653 patients and 1,217 controls were recruited over 4 years in Ireland, Italy, and the Netherlands.

Adequate adjustments for age, education, study site, smoking, alcohol, and physical activity were done before determining the plausible association between female hormones and the risk of developing ALS. The use of oral contraceptive use was higher amongst controls and a dose-response effect was noted. Hormone replacement therapy (HRT) was associated with a reduced risk of ALS only in the Netherlands.

The study demonstrated an association between exogenously administered estrogens and progestogens and the reduced odds of the development of ALS in women. These results were at variance with the existing literature probably because of differing regulatory, social, and cultural attitudes toward pregnancy, birth control, and HRT across the globe. The authors concluded that hormonal factors may be important etiologic factors in the development and progression of ALS. The observation, although interesting, requires a full understanding of the pathophysiological basis with evidence to bring about an actual change in clinical practice in the management of this disease.

Contributed by Dr. Aastha Takkar

Burbulla LF, et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease. Science 2017;357:1255-61.

The quest to understand the pathogenesis of Parkinson's disease so that newer targets for treatment are identified is crucial for researchers. The role of mitochondrial and lysosomal dysfunction has been proposed as the hallmark of substantia nigra dopamine cell damage, but the exact mechanism is still not known. In this study, the authors studied the dopaminergic neurons derived from patients with idiopathic and familial Parkinson's disease. The authors were able to elucidate a time-dependent cascade of the pathological effects starting from oxidative stress in mitochondria to reduced glucocerebrosidase enzyme activity, and finally alpha-synuclein deposition. The authors noted these changes in humans and not mice. Thus, in this study, the authors successfully showed the role of dopamine oxidation as an important link between the lysosomal dysfunction and mitochondrial dysfunction in Parkinson's disease.

Contributed by Dr. Ravi Yadav

Miyamoto K, et al. Causal neural network of metamemory for retrospection in primates. Science 2017;355:188-93.

This interesting work envisaged to study the "metamemory" circuits which enables us to collect strategic and efficient information based on the past experiences. The centers that implement this memory are not known. The authors investigated the neural substrate of metamemory in macaque monkeys by performing cognitive tests and functional magnetic resonance imaging. They identified the prefrontal area 9 along with area 6 in this context. The findings of this study show that there are parallel metamemory circuits that overview the recognition networks for recent and remote memory although they do not have any role in recognition themselves.

Contributed by Dr. Ravi Yadav

Athauda D, et al. Exenatide once weekly versus placebo in Parkinson's disease: A randomised, double-blind, placebo-controlled trial. Lancet 2017. pii: S0140-6736(17)31585-4. doi: 10.1016/S0140-6736 (17)31585-4.

This study may be an important study for neurologists awaiting the neuroprotective therapies that may be utilized in the treatment for Parkinson's disease. The neuroprotective effect of exenatide, which is a glucagon-like peptide-1 (GLP-1) receptor agonist, has been found in preclinical studies conducted on patients suffering from Parkinson's disease. This was a single center randomized double-blind placebo controlled trial which recruited patients between 25-75 years of age, in the Hoen and Yahr stage 2.5 or less and diagnosed as per the Queen Square Brain Bank criteria. The patient received subcutaneous injections of exenatide 2 mg or a placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period. The primary outcome measure was the adjusted difference in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) in the practically defined off-medication state at 60 weeks. Out of the 62 patients recruited, 32 were in the exenatide group and 30 in the placebo group. At the end of the study at 60 weeks, the MDSUPDRS scores improved by 1 point in the treatment group and worsened by 2.1 points in the placebo group. This study showed the beneficial effects of exenatide in improving the MDSUPDRS scores. This study has encouraging findings, and thus, there is a need for further validation of these findings in larger clinical trials. It was not known if the beneficial effect was due to the effect of the medication in amelioraintg the symptomatic effects of the disease.

Contributed by Dr. Ravi Yadav

Logallo N, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): A phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol 2017;16:781-8.

Tenecteplase is a relatively newer thrombolytic agent with a little advantage over alteplase. In this phase 3 randomised, open-label, blinded endpoint trial, the patients with ischemic stroke who were in the 4.5 hour window period were randomized into the tenecteplase group (given in a dosage of 0.4 mg/kg up to 40 mg) or the alteplase group (given in a dosage of 0.9 mg/kg up to a maximum of 90 mg). The primary outcome was the change in the modified Rankin Scale (MRS) score of 0 to 3 at three months. Eleven hundred patients were randomly assigned to the tenecteplase (n = 549) or alteplase (n = 551) groups. The primary outcome was achieved in 64% patients in the tenecteplase group as compared to 63% in the alteplase group. The frequency of serious side effects was similar between the two groups. Tenecteplase was not found superior to alteplase in this study.

Contributed by Dr. Ravi Yadav

Ory DS, et al. Intrathecal 2-hydroxypropyl-β-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: A non-randomised, open-label, phase 1-2 trial. Lancet 2017. pii: S0140-6736 (17) 31465-4. doi: 10.1016/S0140-6736(17)31465-4.

Niemann-Pick disease type C1 is a rare progressive lysosomal neurodegenerative disorder. In preclinical studies, it has been shown that 2-hydroxypropyl-β-cyclodextrins (HPβCD) significantly delays the Purkinje cell loss. In this study, monthly intrathecal HPβCD injections were given and doses of 50, 200, 300, or 400 mg per month were used. Also, the highest dose of 900 mg was used in one patient. Cerebrospinal fluid biomarkers were also evaluated to look for the response. The biomarker response showed that cholesterol metabolism had improved. The patients who completed the study showed a slow disease progression with a stable side-effect profile. This study paves the way for a randomized, double-blind trial to show the actual improvement that takes place with this medication.

Contributed by Dr. Ravi Yadav

Cilia R, et al. Mucuna pruriens in Parkinson disease: A double- blind, randomized, controlled, crossover study. Neurology 2017; 89: 432-8.

Levodopa remains the gold standard in the pharmacological treatment of idiopathic Parkinson's disease. Mucuna pruriens (MP) is a leguminous plant grown in tropical countries whose seeds contain high concentrations of levodopa. Investigators in this trial examined the efficacy and safety of non-pharmacologically processed powder of MP from roasted seeds. Eighteen patients with advanced Parkinson's disease received the following treatment in random sequence: Levodopa plus benserazide (3.5mg/kg); high dose MP (17.5 mg/kg); low dose MP (12.5 mg/kg); Levodopa without benserazide (17.5 mg/kg); MP plus benserazide (3.5 mg/kg). The authors found that when compared with levodopa and benserazide, MP low dose showed a similar motor response but with fewer adverse effects and dyskinesias, while MP high dose induced greater improvement at 90 minutes and 180 minutes, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), greater ON time and fewer adverse effects. Future studies with large sample size are needed before the efficacy and safety of this indigenous product is established for clinical use.

Contributed by Dr. Sahil Mehta

Andersen G, et al. The antimyotonic effect of lamotrigine in non-dystrophic myotonias: A double-blind randomized study. Brain 2017; 140: 2295-305.

Myotonia is a disabling symptom seen in various channelopathies. Mexiletine, a sodium channel blocker is a drug with proven efficacy in non-dystrophic myotonias. The authors of this double-blind placebo controlled randomized study investigated the potential role of lamotrigine in non-dystrophic myotonias, another sodium channel blocker which prolongs the refractory period of voltage-gated sodium channels. Twenty-six patients with genetically confirmed myotonia congenita and paramyotonia congenita were recruited. Lamotrigine in a dose of 150 and 300 mg effectively reduced myotonia as measured by the Myotonic Behaviour Scale compared to the placebo at 8 weeks. Only one patient developed allergic reaction to lamotrigine. Lamotrigine is a good alternative to mexiletine because of its easy availability and low cost.

Contributed by Dr. Sahil Mehta

Welter M.L., et al. Anterior pallidal deep brain stimulation for Tourette's syndrome: A randomised, double- blind, controlled trial. Lancet Neurol 2017;16: 610-19.

Dysfunction of motor and associative limbic fronto-striato-thalamo-cortical circuits induce motor and behavioural signs of Tourette's syndrome. Modulation of these circuits by deep brain stimulation (DBS) are being studied to treat this disorder. In this randomised, double blind, placebo controlled trial, 19 patients underwent surgery to implant bilateral anterior globus pallidus electrodes. Seven patients in the active stimulation group and nine in the sham group completed assessment. There was no significant difference in the Yale Global Tic Severity Score at 3 months between the two groups. Further research is needed before the role of DBS and the optimal target location can be finalized in the treatment of refractory Tourette's syndrome.

Contributed by Dr. Sahil Mehta

Capone F, et al. An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke. Sci Rep 2017;7: 12145.

Extremely low frequency magnetic fields (ELF- MF) have been shown to have a direct protective effect on hypoxic damage in neuron- like cells and an anti-inflammatory effect in microglial cells. Six patients underwent ELF- MF treatment within 48 hours of stroke onset. The first three patients were stimulated for 45 minutes/day and the following three patients for 120 minutes/day. No adverse effects were observed during the treatment phase and the follow up phase of 12 months. The clinical condition (changes in modified Rankin's scale score and the Barthel's index) improved in all patients, with slightly more improvement in patients stimulated for a longer period. The lesion volume at 1 month, as assessed on the magnetic resonance imaging, increased in two patients and reduced in one in the low stimulation group, while the volume of the ischemic lesion reduced in all the patients stimulated for 120 minutes. This is the first study to suggest the feasibility of ELF- MF stimulation in acute ischemic stroke patents. Prospective randomized double-blind studies are needed in future to explore the therapeutic potential of this approach in acute ischemic stroke.

Contributed by Dr. Sahil Mehta

Jamjoom AAB et al. Randomized controlled trials in neurosurgery: An observational analysis of trial discontinuation and publication outcome. J Neurosurg 2017;127:857-66.

Modern medicine is highly evidence based. Therefore, we look forward to different randomized controlled trials, the highest level of evidence, to seek answers for various clinical questions that we face. RCTs are often difficult to perform and often not as forthcoming in surgical specialties in general, and neurosurgery in particular, as compared to the medicine specialties. In this context, this article takes an interesting look at the RCTs in neurosurgery with respect to their discontinuation and publication rates. The authors went through 64 RCTs in neurosurgery performed between 2000 and 2012 after having identified them on the website, clinicaltrials.gov. These RCTs had been either completed or discontinued. The authors of this paper also systematically searched if these RCTs were eventually published or not. Interestingly, more than a quarter (26.6%) of these RCTs had to be discontinued early, primarily because of a slow or insufficient participant recruitment. These trials were mainly found wanting with respect to the poor reporting of primary and secondary outcome measures. Of further interest, the authors noted a high level of reluctance for publication of these trial results with only 30% of the completed trials being eventually published. Discontinued trials (P = 0.0002) and to a lesser extent, trials funded by industries (P = 0.57) were more likely to remain unpublished.

Therefore, this article reveals the actual state of affairs of RCTs in neurosurgery over the last decade or so and highlights the significant wastage of resources as well as patient data in the process.

Contributed by Dr. Kuntal Kanti Das

Roffe C, et al. Effect of routine low-dose oxygen supplementation on death and disability in adults with acute stroke: The Stroke Oxygen Study Randomized Clinical Trial. JAMA. 2017;318:1125-35.

Stroke remains a leading cause of neurological morbidity and mortality worldwide. A number of factors are known to affect the outcome of stroke patients, undetected hypoximea in the initial few days after acute stroke being one of them. The null hypothesis of this study was that oxygen supplementation could circumvent this hypoxia induced secondary neurological deterioration in stroke patients and thus could potentially improve the neurological outcomes. Keeping the primary outcome as death and disability (using mRS score) at 90 days after stroke, this 3-arm randomised controlled trial set out to analyze 8003 patients from 136 centers of United Kingdom. These patients had equivocal indications/contraindications for oxygen therapy in the initial 24 hours of stroke. The three arms, randomized 1:1:1, were: continuous oxygen for 72 hours (n = 2668), nocturnal oxygen for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). The authors noted that the odds for oxygen to improve neurological outcome was 0.97 (95% CI, 0.89 to 1.05; P = 0.47), which completely disproved the null hypothesis. No subgroup could be identified that benefited from oxygen. Rather, at least one serious adverse event was noted in the all the groups although there was no significant harm caused by these events. This led the authors to conclude that the practice of prophylactic low-dose oxygen supplementation was ineffective in changing the outcomes in stroke patients.

Contributed by Dr. Kuntal Kanti Das

McDonald CM et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:1489-98.

This study evaluated the role of ataluren, a mutation specific drug aimed at restoring the deficient dystrophin protein in patients with Duchene's muscular dystrophy (DMD). For this purpose, the authors randomized 230 ambulatory children having nonsense mutated DMD and administered ataluren in 115 of them, the remaining half being administered a placebo. The primary endpoint was a change in the 6-minute walk distance (6MWD) from baseline to week 48.

The result suggested a statistically insignificant change in 6MWD from baseline to week 48 between the ataluren-treated patients and the placebo-treated patients (difference 13.0 m [standard error: 10.4], 95% confidence interval − 7.4 to 33.4; P = 0.213). When a subgroup analysis was performed based on the 6MWD, children who could walk between 300-400 meters had statistically significant change in the 48 week score (P =0.007) while children with scores between < 300 meters or > 400 meters showed no significant change. Ataluren was generally well tolerated and most treatment-emergent adverse events were mild-to-moderate in severity with equal number of patients in both the groups (n = 4) developing serious adverse events. Thus, this study proved that ataluren was safe to administer but without any significant proven benefit.

Contributed by Dr. Kuntal Kanti Das, Dr. Ravi Yadav and Dr. Sahil Mehta

Ma Y, et al. Quality of life of patients with spinal metastasis from cancer of unknown primary origin: A longitudinal study of surgical management combined with postoperative radiation therapy. J Bone Joint Surg Am 2017;99:1629-39.

Spinal metastasis represents an important source of morbidity in patients suffering from systemic cancers. A limited life expectancy and often the poor quality of the life determine the treatment decisions in these patients. These patients are treated by a multimodal treatment strategy but surgery with or without radiation therapy remain the major management option. While much information is available on the treatment outcomes in terms of survival, not many studies have evaluated the parameter of quality of life (QOL) in these patients. This study aimed to prospectively explore the impact on the quality of life of these patients after these two modalities had been administered by making a head-to-head comparison between patients undergoing surgery followed by radiotherapy (n = 191), and the radiotherapy only group (n = 96). The instrument utilized by the authors to assess QOL was the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire during a 6-month period. The authors noted significantly higher adjusted quality-of-life scores in the surgery followed by radiotherapy group than in the radiation therapy alone group in each domain of the questionnaire (all P < 0.05). On the subgroup analysis of the surgery group, the authors noted that the scores were higher in the circumferential surgical decompression group as compared to those who underwent a conservative laminectomy.

Contributed by Dr. Kuntal Kanti Das

Weimar C, et al. Safety of simultaneous coronary artery bypass grafting and carotid endarterectomy versus isolated coronary artery bypass grafting: A randomized clinical trial. Stroke 2017;48:2769-75.

Systemic atherosclerosis is a major killer throughout the world affecting predominantly the elderly people. Atherosclerosis typically produces clinical complications by affecting the coronary and the carotid arteries. Many of these patients are candidates for both coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA) at the same time, even though they may be symptomatic for only one of these two conditions. However, the safety and efficacy of these two procedures being performed simultaneously has not been investigated before. In this trial, 129 patients from two major central European countries were randomized with respect to the procedures they underwent, into two groups: Synchronous CEA and CABG, and CABG alone. The patients were symptomatic for coronary artery disease while the carotid occlusion (≥80% according to European Carotid Surgery Trial) was asymptomatic. With the primary end point of this study being the rate of stroke or death at 30 days, the combined surgery group fared worse (stroke occurring in 12/65,18.5%) as compared with patients receiving isolated CABG (stroke in 6/62, 9.7%). Due to the small number of patients reaching the end point of the study, despite an absolute risk reduction of 8.8%, the difference could not reach statistically significant levels (P = 0.12). Similar results were seen at a 1-year follow-up. Therefore, this study results discourage the simultaneous performance of the two procedures until better evidence emanates in the future trials. Until then, CAE must follow CABG in such clinical scenarios.

Contributed by Dr. Kuntal Kanti Das

Moon K, et al.; Changing paradigms in the endovascular management of ruptured anterior communicating artery aneurysms. Neurosurgery 2017;81:581-4

Anterior communicating artery aneurysms (ACoA) were considered challenging and were deemed unsuitable for coil embolization during the Barrow Ruptured Aneurysm Trial (BRAT). The main reasons attributed were an unfavorable dome-to-neck ratio and a small size of the aneurysm. However, due to phenomenal advances in coil and adjunct endovascular hardware technology, it is currently possible to treat difficult aneurysms with reasonable safety. The authors compared patients treated by coil embolization for ruptured ACoA aneurysms during the trial to those treated after the trial, to determine whether technological advances have actually changed the treatment results. All BRAT (2003-2007) and post-BRAT (2007-2012) ruptured ACoA patients who underwent coil embolization were reviewed. Both groups were comparable in terms of sex ratio, Hunt and Hess grade and mean aneurysm size. The post- BRAT cohort consisted of a higher proportion of complex aneurysms with a wide neck. Consequently, balloon remodeling was used more often. The authors did not find significant difference in the clinical outcome or the retreatment rate between the 2 cohorts and concluded that ruptured ACoA aneurysms, which were previously considered as being unamenable to endovascular therapy could be successfully coiled in the current era with increased use of adjunctive techniques. Their experience has opened the doors for consideration of endovascular treatment of these aneurysms.

Contributed by Chirag K Ahuja

Groves AP, et al.; Acute management and outcomes of iatrogenic dissections during cerebral angiography. J Neurointerv Surg 2017;9:499-501

Cerebral angiography, like any other interventional technique, carries some procedural risks. Iatrogenic dissection is a known complication of this procedure, the management and prognosis of which has not been evaluated in detail in the medical literature. The authors have highlighted their experience with cerebral angiography to determine the incidence of iatrogenic dissections along with clinical outcomes. They evaluated over 17,000 cerebral angiograms (3,933 interventional procedures and >13,000 diagnostic angiograms) over a 13- year duration. The incidence of iatrogenic dissection was low (0.39%), with vertebral artery being the most commonly dissected vessel (49/68, 72%). Nearly all patients (98.5%) were managed conservatively with either no treatment or medical therapy alone being administered. Only 1 patient required stent placement due to critical flow limitation. Two adverse events were noted, of which, only one was symptomatic, with a small infarct in the corresponding territory. Cerebral angiography is thus a safe procedure and carries a miniscule risk of iatrogenic dissection and almost all such patients can be safely managed with conservative management.

Contributed by Chirag K Ahuja

Tsivgoulis G, et al.; Endovascular thrombectomy with or without systemic thrombolysis? Ther Adv Neurol Disord 2017;10:151-160

The successful results of endovascular thrombectomy (ET) have caused a paradigm shift in the management of emergent large vessel occlusion (ELVO). Controversy, however, exists regarding whether pretreatment with intravenous thrombolysis (IVT) should first be offered to all eligible patients prior to ET or the patients should be directly subjected to ET. The present study has addressed this debate by performing a meta-analysis of the included subgroups from randomized controlled trials (RCTs) to evaluate the comparative efficacy between direct ET without IVT pretreatment and bridging therapy (IVT and ET) in patients with ELVO. A large cohort extracted from 7 RCTs was analysed. The results indicated that patients receiving bridging therapy (IVT followed by ET) had lower rates of 90-day death/severe dependency compared with patients receiving only ET. Moreover, patients receiving IVT and ET had a trend towards higher 90-day functional independence rates compared with patients undergoing only ET. This is an indication that IVT and ET are complementary therapies and that bridging with IVT may have added benefit to that of ET alone in such patients. Larger randomized control trials are, however, warranted to prove or disprove this notion.

Contributed by Dr. Chirag K Ahuja

Lal BK, et al. Asymptomatic carotid stenosis is associated with cognitive impairment. J Vasc Surg 2017;66:1083-92

It is well recognised that hypertension, coronary artery disease and stroke can lead to vascular cognitive impairment. The authors have aimed to evaluate the isolated impact of asymptomatic carotid stenosis on cognitive function. Two matched cohorts of 82 patients (with > 50% asymptomatic carotid stenosis) and 62 controls (without stenosis) were analysed regarding their clinical neurologic data, National Institutes of Health Stroke Scale scores, and comprehensive neuropsychological profile. The assessment of carotid stenosis and plaque area was made by comprehensive Doppler ultrasound with B-mode imaging. Transcranial Doppler (TCD) was used for measuring breath-holding index (BHI) and microembolization. The patients in the stenosis group had worse composite cognitive scores and domain-specific scores for learning and memory as well as for motor and processing speed. The patients in the stenosis group with reduced BHI (50% of them) performed worse than others in that group. However, there was no correlation of cognitive function with measures of plaque burden (degree of stenosis, least luminal diameter, and plaque area). The mechanism is likely to be hemodynamic, as evidenced by reduced cerebrovascular reserve with resultant hypoperfusion secondary to carotid stenosis in the presence of inadequate collateralization. These findings have the potential to initiate a debate on whether or not asymptomatic > 50% carotid stenosis should be considered for stenting or endarterectomy.

Contributed by Dr. Chirag K Ahuja

Brinjikji W, et al.; The effects of statin therapy on carotid plaque composition and volume: A systematic review and meta-analysis. J Neuroradiol 2017;44:234-40.

Statins have proven to lower blood cholesterol levels and consequently have been proposed to stabilize and diminish atherosclerotic lesions. An interesting objective evaluation of the effect of statin use on carotid plaque composition, as assessed by the serial high-resolution carotid plaque magnetic resonance imaging (MRI) scan, has been done. Following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) approach, the authors have performed a meta-analysis of the effects of statin therapy on lipid-rich-necrotic-core (LRNC) volumes, wall volumes and lumen volumes of carotid plaques. From the 326 articles initially chosen from the online science libraries, seven studies have been included with 361 patients who were on statin therapy. All patients were imaged using serial high-resolution carotid plaque MRI (magnet strengths of 1.5 or 3 Tesla only). The following outcomes were analysed: Lipid-rich necrotic core (LRNC) volume, wall volume and lumen volume at various intervals up to 1 year. They reported no significant change in the carotid wall volume or lumen volume. The LRNC volume, however, showed a significant decrease at 12 months. This objectively proved that statin therapy not only reduces the circulating cholesterol levels but is also associated with significant reductions in LRNC of the atheromatous plaque at a 1-year interval. This finding, however, did not translate to a reduction in the carotid wall volume and, hence, the degree of luminal stenosis.

Contributed by Dr. Chirag K. Ahuja

Choi HH, et al. Comparison of clinical outcomes of intracranial aneurysms: Procedural rupture versus spontaneous rupture. AJNR Am J Neuroradiol. 2017. doi: 10.3174/ajnr.A5344.

Endovascular coiling is a minimally invasive treatment option for intracranial aneurysms. Intraprocedural rupture of the aneurysm, however, is a devastating complication. The authors have aimed to evaluate the clinical outcomes of patients with the procedural rupture of unruptured saccular intracranial aneurysms compared with those who had a spontaneous rupture of the aneurysms over a 5-year duration. One cohort consisted of 1340 patients (harbouring 1595 unruptured saccular aneurysms), and the other of 198 patients who presented with unruptured aneurysms. Procedural rupture developed in 19/1340 (1.4%) patients, and the morbidity rate related to the procedural rupture was 26.3%, with no mortality. The Hunt and Hess scale grades and the hospitalization days of patients with a procedural rupture were equivalent to those of patients presenting with spontaneous aneurysmal rupture. Subsequent treatment procedures after hemorrhage (including a lumbar drainage, an extraventricular drainage, a decompressive craniectomy, and a permanent shunt) showed no difference between the 2 groups. However, the hemorrhage volumes were smaller in the procedural-rupture group with less requirement of vasospasm therapy. The procedural-rupture group fared well at a 6-month follow-up duration with better modified Rankin scale scores. Inspite of procedural rupture during aneurysm embolization, these patients tend to do better than the spontaneously ruptured group.

Contributed by Dr. Chirag K. Ahuja

Pierot L, et al.; Safety and efficacy of aneurysm treatment with the WEB: Results of the WEBCAST 2 study. Am J Neuroradiol 2017;38:1151-55

The woven endobridge (WEB) device is a conceptual alternate of platinum coils for the endovascular treatment of wide-necked bifurcation aneurysms. It has been modified for better visualization of the aneurysmal neck. The WEB Clinical Assessment of IntraSaccular Aneurysm Therapy (WEBCAST) 2 study evaluated the single-layer versions of the device. The eligible patients having a wide-necked bifurcation aneurysm for which WEB treatment was possible, were included. The clinical data including adverse events were analysed at 1 month and 1 year following the procedure. Ten European neurointerventional centers included 55 patients with 55 aneurysms (middle cerebral artery: 45.5%, anterior communicating artery: 29.1%, basilar artery: 16.4% and internal carotid artery terminus: 9.1%). The procedural morbidity and mortality at 1 month were 1.8% and 0.0%, respectively. The morbidity and mortality at 1 year were 3.9% and 2.0%, respectively. Complete occlusion was observed in 27/50 aneurysms (54.0%) at 1 year, with a neck remnant being observed in 13/50 (26.0%), and an aneurysmal remnant in 10/50 (20.0%) patients. The WEBCAST 2 study thus confirmed the safety and efficacy of aneurysm treatment with the WEB device.

Contributed by Dr. Chirag K. Ahuja

Arhuidese IJ, et al. Outcomes of primary and secondary carotid artery stenting. Stroke 2017; STROKEAHA.117.016963. https://doi.org/10.1161/STROKEAHA.117.016963

The authors compared 8519 cases of primary carotid artery stenting (CAS) with 2645 cases of CAS after prior ipsilateral carotid endarterectomy (CASAPICEA) and 578 cases of redo CAS. The 30-day stroke/death rate was 2.5% versus 2.0% versus 1.3% for asymptomatic patients (P = 0.23); and, 5.2% versus 2.6% versus 5.0% for symptomatic patients (P = 0.003). A significantly lower 30-day stroke/death rate was associated with CASAPICEA as compared to primary CAS among symptomatic patients. The odds of bradycardia and hypotension were significantly lower following CASAPICEA and redo-CAS groups as compared to primary CAS. There were no significant differences in the hazards of stroke/death at 1 year for CASAPICEA and redo-CAS as compared with primary-CAS. The authors concluded that CASAPICEA is associated with lower odds of stroke/death in the peri-procedural period in symptomatic cases as compared to primary CAS. Lower odds of hypotension and bradycardia were seen in CASAPICEA and redo-CAS as compared to primary CAS.

Contributed by Dr. Anant K. Mehrotra

Galea JP, et al. Predictors of outcome in aneurysmal subarachnoid hemorrhage patients. Observations from a multicenter data set. Stroke 2017; strokeaha. 117.017777 https://doi.org/10.1161/strokeaha. 117.017777

The authors studied 3341 patients of subarachnoid haemorrhage due to aneurysmal rupture. The median age at the time of presentation was 55 years. 2288 out of 3341 (68.5%) were female patients. Majority of patients presented in a good World Federation of Neurosurgical Societies (WFNS) grade (grade 1 and 2) [2397/3341;70%] and 2600 (75%) patients were treated by endovascular coiling. An increasing age, the WFNS grade, the preoperative rebleeding episode, the need for cerebrospinal fluid diversion and the presence of delayed cerebral ischemia were the independent predictors of an unfavourable outcome. The authors concluded that the potentially modifiable risk factors of delayed cerebral ischaemia and preoperative rebleeding are associated with an unfavourable outcome.

Contributed by Dr. Anant K. Mehrotra

Petzold A, et al. Retinal layer segmentation in multiple sclerosis: A systematic review and meta-analysis. Lancet Neurol 2017; 16: 797-812

The authors conducted a systematic review and meta-analysis to assess the retina in patients suffering from multiple sclerosis with or without optic neuritis. The authors classified the data into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). Of the 25,497 records identified, 110 articles were eligible and 40 reported data on a total of 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls that met the published optical coherence tomography (OCT) quality control criteria and were suitable for meta-analysis. The peripapillary retinal nerve fibre layer (RNFL) showed thinning in the MSON eyes and MSNON eyes as compared to the control eyes. The macula showed RNFL thinning of -6.18 μm (range:-8.07 to -4.28; P < 0.0001) in the MSON eyes, and -2.15 μm (range: -3.15 to -1.15; P < 0.0001) in the MSNON eyes compared with the control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) resulted in -16.42 μm (-19.23 to -13.60; P < 0.0001) thickness for the MSON eyes, and -6.31 μm (-7.75 to -4.87; P < 0.0001) thickness for the MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in the MSON eyes compared with the control eyes (0.77 μm, 0.25 to 1.28; P = 0.003). No statistical difference was found in the thickness of the combined outer nuclear layer and outer plexiform layer when the MSNON or MSON eyes were compared with control eyes, but a small degree of thickening of the combined layer was present in the MSON eyes, when the MSON eyes were compared with the MSNON eyes.

Contributed by Dr. Anant K. Mehrotra

Zhang S, et al. Decompressive craniectomy in hemorrhagic cerebral venous thrombosis: Clinicoradiological features and risk factors. J Neurosurg 2017;127:709-15

Fifty-eight cases of cerebral venous thrombosis (CVT) who underwent decompressive craniectomy were included in the study and their clinical and radiological features as well as surgical outcomes were retrospectively analysed. Their mean age was 39.7 + 12.5 years with the majority of cases being female patients (39; 67.2%). The mean duration from symptom onset to surgery was 3.3 ± 1.9 days, and 21 patients experienced an acute course. The mean mass lesion volume was 114.7 ± 17.7 ml. According to their hemorrhagic proportion, cases were divided into the hemorrhage-dominated (27 [46.6%]) and the edema-dominated (31 [53.4%]) groups. After 6 months of follow-up, 56.9% of patients had achieved a favorable outcome, and 8 patients had died. The hemorrhage-dominated lesions (P = 0.026) and deep cerebral venous involvement (P = 0.026) were significantly associated with a poor outcome. The authors concluded that DC is an effective life-saving treatment in the cases suffering from severe haemorrhagic CVT.

Contributed by Dr. Anant K. Mehrotra


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Online since 20th March '04
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