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Table of Contents    
NI FEATURE: THE FOURTH DIMENSION - COMMENTARY
Year : 2015  |  Volume : 63  |  Issue : 2  |  Page : 250-254

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


Department of Neuro and Spine Surgery, Institute of Neurosciences and Spinal Disorders, Global Hospitals and Health City, Perumbakkam, Chennai, Tamil Nadu, India

Date of Web Publication5-May-2015

Correspondence Address:
Prof. K Sridhar
Head Department of Neuro and Spine Surgery, Director, Institute of Neurosciences and Spinal Disorders, Global Health City, 439, Cheran Nagar, Perumbakkam, Off OMR, Sholinganallur Tambaram Highway, Chennai - 600 100, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.156294

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How to cite this article:
Sridhar K. A summary of some of the recently published, seminal papers in Neuroscience. Neurol India 2015;63:250-4

How to cite this URL:
Sridhar K. A summary of some of the recently published, seminal papers in Neuroscience. Neurol India [serial online] 2015 [cited 2019 Aug 17];63:250-4. Available from: http://www.neurologyindia.com/text.asp?2015/63/2/250/156294


Besharati Tabrizi L, Mahvash M. Augmented reality-guided neurosurgery: Accuracy and intraoperative application of an image projection technique. J Neurosurg 2015 Mar 6:1-6

An augmented reality system has been developed for image-guided neurosurgery. It projects, in real time, images with regions of interest onto the patient's head, skull, or brain surface. The authors evaluated the system during surgery in 5 patients and compared the results with that of a standard navigation system. They found the system to be accurate and feel that this would greatly enhance the accuracy and improve planning of neurosurgical procedures.

Martirosyan NL, et al. Microsurgical anatomy of the arterial basket of the conus medullaris. J Neurosurg Spine 2015 Mar 6:1-5

The conus medullaris is a very important and a compact region of the spinal cord. Attention to the blood supply of this region has not been the subject of focus in the past. In order to study the microsurgical anatomy of the arterial basket of the conus medullaris, the authors performed microsurgical dissections of 16 formalin fixed spinal cords within 48 hours of the subject's death. The arterial basket represents a critical anastomotic structure between tha anterior spinal atery and the posterior spinal artery. It augements the blood supply to the spinal cord and participates in vascular pathologies of the region. It is, therefore, imperative for the surgeons involved in treating pathologies of this region to read this work.

Mokin M, Levy EI. Guest Editorial: Endovascular Treatment of Acute Ischemic Stroke: What's Next? Neurosurgery 76:235-238,2015

Mokin and Levy, in their guest editorial, focus on the current status of neurointervention in acute stroke. The findings of the MR-CLEAN trial that were presented at the 9 th World Stroke Congress, as well as the ESCAPE and SWIFT PRIME trials, establish the important role of an early endovascular intervention in patients suffering from a large vessel stroke in obtaining a good patient outcome. The current thrombectomy devices achieve recanalization and reperfusion rates that approximately range from 80 to 95%. The authors state that "Changing the status of endovascular stroke therapy from experimental to recommended would also have profound implications for the organization of acute stroke care networks on both the national and local levels because comprehensive stroke centers further assume a leadership position in providing care for thrombectomy-eligible patients." While recanalization and reperfusion are associated with a good neurological outcome, the authors wonder why the rates of favorable outcomes even with modern devices are still approximately twice as low as the rates of successful recanalization. They feel that "Involving emergency medical services personnel in the recognition of stroke patients who are potential candidates for intra-arterial interventions, developing acute stroke protocols for emergency room personnel, and mobilizing the neurointerventional team early, are some promising ways of reducing the time to initiation of intra-arterial reperfusion therapies." The timing of angiographic reperfusion is very important in determining a good neurological outcome. It is, therefore, important to reduce the time taken at each level right from the femoral puncture to the establishment of reperfusion. The authors also discuss the possible use of neuroprotection as a technique to increase the window period during which a good outcome is possible by the establishment of successful reperfusion.

Campbell BC, et al and all EXTEND-IA Investigators.Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009-18

Endovascular therapy for ischemic stroke has been reported to produce variable results. Campbell and co-workers in a randomized study compared in patients, who underwent treatment in less than 4.5 hours after the onset of ischemic stroke, the effects of either undergoing endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. The patients included in the study had either occlusion of the internal carotid or middle cerebral artery, presence of salvageable brain tissue and an ischemic core of less than 70 ml on computed tomographic perfusion imaging. The outcome was measured by assessing reperfusion within 24 hours, early neurological improvement and improvement in functional score at 90 days. The percentage of ischemic territory that had undergone reperfusion at 24 hours was significantly more in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%) with remarkably improved functional outcome at 90 days. These results, by many experts, were considered a major advancement in the field of stroke management. Results were so significant in favour of the combination therapy that randomisation of patients in the group that was undergoing treatment with alteplase alone was considered inappropriate and the trial was stopped prematurely.

Contributed by: Dr. Ravindra Kumar Garg, Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow 226003, India

Ekstam L, et al. The combined perceptions of people with stroke and their carers regarding rehabilitation needs 1 year after stroke: A mixed methods study. BMJ Open 2015;5:e006784

Rehabilitation after stroke should generally be based on the needs of the person with the stroke. However, in different studies, 33-49% of stroke patients felt unmet rehabilitation needs at one year after the stroke. Ekstam et al looked at associations between the dyad's (two individuals regarded as a pair; person with stroke and the informal caregiver) perception of the rehabilitation needs of a person with stroke and the stroke severity, personal factors (gender, age, sense of coherence), the use of rehabilitation services, the amount of informal care and the caregiver's burden. 86 persons with stroke (mean age 73 years, 38% women) and their caregivers (mean age 65 years, 40% women) were enrolled in the study after exclusions. Fifty-two per cent of the dyads (person with stroke and informal caregiver)perceived that the person with stroke's need for rehabilitation was met 12 months after the stroke. Met rehabilitation needs were associated with less severe stroke, more coping strategies for solving problems in everyday activities and less caregiver's burden.

Chen R, et al. Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas. Neurosurgery Focus 38(3): E2, 2015

The molecular markers in Low Grade Gliomas (LGG) have currently assumed an important role in the management strategies of these tumors. Recent advances have led to a better understanding of how molecular, genetic and epigenetic alterations influence the pathogenesis of different histological grades of gliomas, leading to the possibility of better targeted surgical and medical therapies. Laboratory testing of molecular features including the IDH status, 1p19q co-deletion, and MGMT promoter methylation has offered new insights regarding their prognosis and management, including the prediction of their response to chemotherapy and radiation treatment.

In contrast to the glioblastomas (GBMs), majority of the LGGs harbor mutations of IDH genes, especially of IDH1. This has led to the hypothesis that an IDH1-mutant GBM represents a malignant transformation of an undiagnosed LGG, and an IDH1-wild-type GBM is, in many ways, a different class of the disease, although sharing the same histological features. IDH1 genetic mutation is thought to be an early and perhaps the initiating event leading to tumor development. Primary GBMs are now thought to be IDH1 wild-type GBMs; while secondary GBMs are considered as arising from LGGs with an IDH mutation. The primary GBMs behave quite differently from their IDH1-mutant counterparts (the secondary GBMs), with a later age of onset, a worse prognosis, and a distinct imaging characteristics. An IDH wild-type LGG tends to possess a more aggressive clinical behaviour quite similar to that of a GBM. The absence of IDH mutation in a LGG or an intermediate glioma perhaps portends a graver prognosis than a GBM with an IDH mutation.

IDH, MGMT and other markers exhibit varying degrees of correlation and prognostic influence. Their effects can also be independent and additive. It is expected that the subsequent WHO classifications will include the molecular subtyping which will form the basis of treatment of gliomas in the future.

Kuchcinski G, et al. Three-tesla functional MR language mapping. Comparison with direct cortical stimulation in gliomas. Neurology 84:560-568, 2015

The authors evaluated the accuracy of functional magnetic resonance imaging (fMRI) at 3 Tesla in the pre-operative localization of language areas. The fMRI localization was compared to direct cortical stimulation done during surgery with the patient awake. A site by site comparison was performed. The authors concluded that there were pitfalls in the currently used fMRI localization of language areas especially in the cases involving high grade gliomas or hyperperfused regions of the brain.

Ille S et al. Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation. J Neurosurg 2015 March 6:1-14

The authors in this study studied the predictive value and specificity of repetitive navigated transcranial magnetic stimulation in the pre-operative mapping of language areas of the brain. They also proposed a protocol for the use of the navigated transcranial magnetic stimulation. They found that navigated transcranial magnetic stimulation was more sensitive than functional magnetic resonance imaging in mapping language areas. It was, however, less specific than direct cortical stimulation. They also found that the combination of functional magnetic resonance imaging and navigated transcranial magnetic stimulation was more accurate in language mapping than either one of them performed individually.

Huang YL, et al. Susceptibility-weighted MRI in mild traumatic brain injury. Neurology 84:580-585, 2015

Patients suffering from mild traumatic brain inury patients often recover without any lasting neurological deficits. However, there is a significant proportion of patients who suffer from significant cognitive disabilities following mild traumatic brain injuries. Huang et al studied the presence of microbleeds in the brain in these patients using the susceptibility weighted MRI sequences and found short-term memory disturbances in patients with microbleeds. They conclude from their study that the presence of microbleeds is a potential biomarker for the severity of the brain injury and should probably be used in patients with mild traumatic brain injury.

Lubelski D, et al. Depression as a predictor of worse quality of life outcomes following nonoperative treatment for lumbar stenosis. J Neurosurgery: Spine 22: 267-272, 2015

The authors studied the role of depression in the post-treatment quality-of-life (QOL) in 502 patients treated conservatively for lumbar spinal stenosis and claudication. They found in their assessment 4 months following the treatment that severely depressed patients have significantly less improvement in their QOL when compared to those with little or no depression. It is also interesting to note that the same was the result for patients who underwent fusion surgery for lumbar spinal stenosis. Depression would, therefore, need to be addressed aggressively in these patients for achieving a good outcome.

Domenicucci M, et al. Vincenzo Quercioli (1876-1939), researcher and pioneer of the  Atlas More Details fracture. J Neurosurg Spine 22: 253-258, 2015

Jefferson has been credited with the description of the fractures of atlas. However, in his seminal paper, he appears to have alluded to the work of Vincenzo Quercioli. A review of the work in the early 20 th century on atlas fractures led Domenicucci et al to discover the work of Prof Vincenzo Quercioli, who in 1908 wrote on fractures of the atlas in Italian language. The paper described the first case of a quadripartite fracture of the atlas, and it accurately reported the mechanism of injury, symptoms, neurological examination, treatment, complications, and cause of death of the patient. Quercioli performed an autopsy on the patient and described the pathological anatomy of the fracture. He even postulated that axial force was the causation of the injury.

Finnerup NB, et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurology 14: 162-173, 2015

The Special Interest Group on Neuropathic Pain (NeuPSIG) performed a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. 229 studies were included in the meta-analysis. The findings permitted a strong recommendation for use and proposal as first-line treatment in neuropathic pain, for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line, for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line, for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only.

Garcia HH, et al. Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: A double-blind, randomised controlled trial. Lancet Infect Dis 2014;14:687-95

Treatment with the available antiparasitic drugs has consistently been reported to be effective in reducing the central nervous system parasitic load in patients with neurocysticercosis. Unfortunately, the treatment with the individual antiparasitic drugs, albendazole and praziquantel, fails to produce complete eradication of the parasites from the brain in the majority of the patients undergoing treatment. Garcia and colleagues performed a randomized controlled study where they used a combination of albendazole and praziquantel in one arm and varying dose regimens of albendazole in the other two arms to see their effects in eradicating multiple parasitic cysts from the brain. The combination of albendazole and praziquantel was successful in eliminating parasites from the brain in 64% of the patients when compared with 37% in the standard albendazole dosage group and 53% in the increased albendazole dosage group. Although, seizures were less frequent in patients with complete resolution of the brain lesions, these patients could not achieve a completely seizure-free state despite complete resolution of parasites from the brain. Thus, even this combination of albendazole and praziquantel is far from ideal. This study suggests that combining of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without any increase in side-effects. However, the results are still sub-optimum. Thus, there is an urgent need for more effective antiparasitic drugs that help in improving the long-term prognosis of patients with neurocysticercosis.

Contributed by: Dr. Ravindra Kumar Garg, Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow 226003, India.

Witsch J, et al.Intraventricular hemorrhage expansion in patients with spontaneous intracerebral hemorrhage.Neurology 2015;84:989-94

Intraventricular hemorrhage is usually reported secondary to rupture of a parenchymal hemorrhage into the ventricles or can occur from a primary vascular disorder of the brain like an arteriovenous malformation or an aneurysm. Thalamic and caudate hypertensive haemorrhages have the highest incidence of developing an intraventricular haemorrhage. Hydrocephalus, developing as a sequel to an IVH, may require a ventricular drainage procedure. Witsch and co-workers studied the clinical differences between the initial intraventricular haemorrhage seen at the time of admission and the delayed intraventricular haemorrhage in due course of illness following the hospital admission. In patients with spontaneous intracerebral haemorrhage (ICH), 53.5% had an intraventricular haemorrhage on the initial CT scan while 14.5% developed intraventricular haemorrhage after the initial CT scan was done. The increase in ICH volume was larger in patients who developed a delayed IVH when compared to those patients who had either no IVH or IVH present at admission CT scans. They noted that the initial intraventricular haemorrhage has a worse functional long-term outcome in comparison to that of delayed intraventricular haemorrhage. The importance of this study lies in the emerging knowledge that the initial intraventricular haemorrhage often needs an aggressive treatment.

Contributed by: Dr. Ravindra Kumar Garg, Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow 226003, India.

Yarnykh VL, et al. Fast whole-brain three-dimensional macromolecular proton fraction mapping in multiple sclerosis. Radiology 274:210-220, 2015

The authors evaluate the clinical utility of fast macromolecular proton fraction (MPF) brain mapping in multiple sclerosis (MS) and compare it to the MR imaging measures of tissue damage including magnetization transfer (MT) ratio and relaxation rate (R1). They concluded that MPF mapping enables quantitative assessment of demyelination in the normal-appearing brain tissues and shows the primary clinical relevance of gray matter damage in MS.

Cudkowicz ME, et al. Ceftriaxone Study Investigators.Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: A multi-stage, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2014;13:1083-91

Amyotrophic lateral sclerosis (ALS) is the most frequent degenerative disease in India affecting virtually persons of all ages. Patients usually die within 2-5 years of the onset of symptoms. Riluzole is currently the only drug available that provides minor benefit and increases survival for a few months. Some early reports demonstrated the efficacy of ceftriaxone treatment in amyotrophic lateral sclerosis. By interfering with excitatory amino acid transporter 2 (EAAT2) expression, ceftriaxone may decrease glutamate excitotoxicity that may have a role to play in the pathophysiology of ALS. Cudkowicz and his colleagues performed a multi-stage, randomised, double-blind, placebo-controlled trial. The trial was conducted in three stages. In stages 1 (pharmacokinetics) and 2 (safety), the participants were randomly assigned to ceftriaxone (2 g or 4 g per day) or a placebo. In stage 3 (efficacy), the participants assigned to ceftriaxone in stage 2 received 4 g of ceftriaxone, participants assigned to placebo in stage 2 received a placebo, and new participants were randomly assigned to 4 g ceftriaxone or a placebo. Overall, ceftriaxone in amyotrophic lateral sclerosis did not show clinical efficacy. No significant differences in survival between the groups were recorded in stage 3. During stages 1 and 2, the mean Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score declined a bit gradually in participants who received 4 g ceftriaxone than in those on placebo, but in stage 3, the functional decline rates between the treatment groups did not differ. This phase-3 ceftriaxone study, which was started with great hope, failed to produce any clinical benefit. Stem cell transplantation may now be the focus of attention to provide a ray of hope for patients suffering from ALS.

Contributed by: Dr. Ravindra Kumar Garg, Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow 226003, India.

Salanova V, et al. Long term efficacy and safety of thalamic stimulation for drug resistant partial epilepsy. Neurology 84:1017-1025, 2015

The authors have reported the long term results of the SANTE trail looking at the efficacy of deep brain stimulation of the anterior nucleus of thalamus in drug resistant partial epilepsy. The report provided Class IV evidence that for patients with drug resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device related adverse event rate at 5 years.

Welch RD, et al. Neurological Emergencies Treatment Trials (NETT) Network Investigators. Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population. Epilepsia 2015;56:254-62

Status epilepticus is defined as a seizure activity that lasts more than 30 minutes. Prehospital treatment is crucial as it can shorten the duration of status epilepticus and therefore help in preventing many systemic and neurological complications of status epilepticus. Welch and co-workers performed a randomized controlled study investigating the effectiveness of intramuscular midazolam versus intravenous lorazepam in treating pediatric patients with status epilepticus in the prehospital care setting. In this multicenter clinical trial, patients diagnosed with status epilepticus were randomised to receive either intramuscular midazolam or intravenous lorazepam administered by paramedics in the prehospital setting. Almost similar number of patients had seizure cessation prior to their arrival to the emergency department. The response time after starting treatment was shorter in children who received intramuscular midazolam. This was mainly due to the fact that it took a shorter time to administer the active treatment in the latter case. The safety profiles of the two medicines and their modes of administration were similar. Results of this study have shown that intramuscular midazolam can be invaluable in stopping seizures in a prehospital setting. These findings are more relevant for countries where access to hospital services is not readily available as intramuscular midazolam can be administered by paramedics with far more ease than intravenous lorazepam.

Contributed by: Dr. Ravindra Kumar Garg, Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow 226003, India.




 

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