MCM6

MCM6

Minichromosome maintenance proteins (MCMs) play an essential role in DNA replication and other cellular activities.

The long term risk of tumor recurrence is higher in adamantine epithelioma (AE) than squamous papillary tumor (SP) and it is associated with MCM6 and DNA topoisomerase II alpha expression 1).

MCM6 protein expression in craniopharyngiomas are related to the prognosis of tumor and thus may be useful in predicting the risk of tumor relapse 2).

In a study, Cai et al., analyzed the relationship between MCM mRNA expression and clinical parameters in 325 gliomas, and found that MCM6 presented high expression and was associated with poor survival. Immunohistochemistry analysis of an independent dataset of 423 glioma tissues confirmed the overexpression of MCM6 protein, especially in glioblastomas (GBMs) with shorter overall survival (OS). Importantly, a combination of MCM6 overexpression with IDH1 mutation further improved the prediction of the prognosis of GBMs. Patients with IDH1 mutation and low MCM6 expression exhibited the longest survival, whereas those with high MCM6 expression and wild-type IDH1 showed the shortest. Collectively, the observation indicates that MCM6 is a biomarker for predicting poor prognosis of the patients with glioma 3).

1)

Xu J, Zhang S, You C, Huang S, Cai B, Wang X. Expression of human MCM6 and DNA Topo II alpha in craniopharyngiomas and its correlation with recurrence of the tumor. J Neurooncol. 2007 Jun;83(2):183-9. Epub 2007 Apr 5. PubMed PMID: 17410335.
2)

Xu JG, You C, Wang XJ, Shuai KG, Wang XS. [Expression of minichromosome maintenance protein 6 in craniopharyngioma and its correlation with prognosis]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Jan;38(1):64-7. Chinese. PubMed PMID: 17294730.
3)

Cai HQ, Cheng ZJ, Zhang HP, Wang PF, Zhang Y, Hao JJ, Wang MR, Wan JH. Overexpression of MCM6 predicts poor survival in patients with glioma. Hum Pathol. 2018 May 9. pii: S0046-8177(18)30154-0. doi: 10.1016/j.humpath.2018.04.024. [Epub ahead of print] PubMed PMID: 29753008.

Decision Making in Neurovascular Disease

Decision Making in Neurovascular Disease

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Neurovascular medicine has emerged as an established, semi-independent subspecialty of neurology and neurosurgery. Decision Making in Neurovascular Disease focuses on the challenging process of determining the best approach for managing patients with intracranial atherosclerosis, carotid artery disease, stroke, aneurysms, arteriovenous malformations, arteriovenous fistulae, cavernous malformations, and hypervascular tumors. Leonardo Rangel-Castilla, Robert Spetzler, esteemed coauthors, and an impressive cadre of experts discuss highly divergent modalities including medical management, open cerebrovascular, endovascular, radiosurgery, and combined/multimodality alternatives.

The book is organized into seven sections: Ischemic Stroke and Vascular Insufficiency, Aneurysms – Anterior Circulation, Aneurysms – Posterior Circulation, Aneurysms – Other, Arteriovenous Malformations and Fistula, Cavernous Malformations, and Hypervascular Tumors. Chapters include an introduction, decision-making algorithm, whether to treat, conservative management, anatomical considerations, clinical and imaging evaluation, differential diagnosis, treatment options, images, clinical and radiographic follow-up, and suggested reading.

Key highlights

Simple algorithms accompanying 71 chapters supported by the latest, most updated information in the literature
More than 375 radiologic images help elucidate disease-specific treatment decision making
Step-by-step guidance, clinical pearls, surgical nuances, complication avoidance, and evidence-based outcomes provide in-depth understanding
Point/counterpoint expert commentary on each case provides balanced insights on potential implications of specific treatments
This essential step-by-step book is a must-have for residents and fellows in neurosurgery, neurology, endovascular, interventional radiology, vascular neurology, and neurocritical care, as well as veteran clinicians in these specialties

Echinococcus canadensis

Echinococcus canadensis

The cestode Echinococcus canadensis belongs to the complex Echinococcus granulosus sensu lato. This parasite is a member of Cyclophyllidea which comprise the majority of tapeworms that are of medical importance. Adult E. canadensis parasitise the small intestines of dogs and other canids. The larval stage is one of the causative agents of the serious and life-threatening human disease cystic echinococcosis. E. canadensis has a worldwide distribution.

A study reports mitochondrial gene analysis from 4 Mongolian pediatric cerebral CE cases. Molecular confirmation was obtained for 3 of the 4 cases, with all 3 cases determined to be due to Echinococcus canadensis (G6/G7) infection. None of the cases had other organ involvement. This is only the third report on the molecular identification of the Echinococcus species responsible for Cerebral echinococcosis, and only the second report of E. canadensis (G6/G7) being the causative agent of cerebral CE 1).

1)

Shirmen O, Batchuluun B, Lkhamjav A, Tseveen T, Munkhjargal T, Sandag T, Lkhagvasuren E, Yanagida T, Nishikawa Y, Ito A. Cerebral cystic echinococcosis in Mongolian children caused by Echinococcus canadensis. Parasitol Int. 2018 May 9. pii: S1383-5769(18)30120-X. doi: 10.1016/j.parint.2018.05.006. [Epub ahead of print] PubMed PMID: 29753095.

Update: Antiepileptic drug treatment outcome

Antiepileptic drug treatment outcome

Careful antiepileptic drug selection for epileptic patients must be highlighted in order to improve outcome, reduce adverse drug reactions (ADRs) and improve patient compliance 1).

The goal in treating patients with epilepsy is a cost-effective approach to the elimination of seizures or a reduction in their number and frequency while avoiding drug interactions and side effects, so as to achieve the best possible quality of life. Among the desirable outcomes are an enhanced understanding of epilepsy by patients, caregivers, and society, and a lessening of the psychosocial risks of this disease. Patients fail to achieve their goals and outcomes when they fail to adhere to the drug regimen or when a less-than-adequate drug regimen is prescribed. To help improve adherence, once- or twice-daily formulations should be used. Working together, patients and clinicians can maximize the effectiveness of AED therapy and the potential for achieving desired goals and outcomes 2).

Despite the availability of many new AEDs with differing mechanisms of action, overall outcomes in newly diagnosed epilepsy have not improved. Most patients who attain control do so with the first or second AED. The probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried. More than one-third of patients experience epilepsy that remains uncontrolled.

This was the conclusion of a longitudinal observational cohort study that was conducted at the Epilepsy Unit of the Western Infirmary in GlasgowScotland. A total of 1795 individuals who were newly treated for epilepsy with AEDs between July 1, 1982, and October 31, 2012, were included in this analysis. All patients were followed up for a minimum of 2 years (until October 31, 2014) or until death, whichever came sooner. Data analysis was completed between March 2015 and May 2016.

Seizure control was assessed at the end of the study period. Probability of achieving 1-year seizure freedom was estimated for each AED regimen prescribed. Multivariable models assessed the associations between risk factors and AED treatment outcome after adjustments were made for demographic and clinical characteristics.

Of the 1795 included patients, 964 (53.7%) were male; the median age was 33 years (range, 9-93 years). At the end of the study period, 1144 patients (63.7%) had been seizure free for the previous year or longer. Among those achieving 1-year seizure freedom, 993 (86.8%) were taking monotherapy and 1028 (89.9%) had achieved seizure control with the first or second AED regimens. Of the total patient pool, 906 (50.5%) remained seizure free for 1 year or longer with the initial AED. If this AED failed, the second and third regimens provided an additional 11.6% and 4.4% likelihoods of seizure freedom, respectively. Only 2.12% of patients attained optimal seizure control with subsequent AEDs. Epilepsy that was not successfully controlled with the first AED had 1.73 times greater odds of not responding to treatment for each subsequent medication regimen (odds ratio, 1.73; 95% CI, 1.56-1.91; P < .001). 3).


Machine learning approaches yielded predictions of successful drug treatment outcomes which in turn could reduce the burdens of drug trials and lead to substantial improvements in patient quality of life 4).

1)

Horváth L, Fekete K, Márton S, Fekete I. Outcome of antiepileptic drug treatment of 1282 patients with epilepsy, their pharmacovigilance reports and concomitant medication on CNS in an East-Hungarian adult database. J Neurol Sci. 2016 Oct 15;369:220-226. doi: 10.1016/j.jns.2016.08.039. Epub 2016 Aug 17. PubMed PMID: 27653893.
2)

Garnett WR. Antiepileptic drug treatment: outcomes and adherence. Pharmacotherapy. 2000 Aug;20(8 Pt 2):191S-199S. Review. PubMed PMID: 10937819.
3)

Chen Z, Brodie MJ, Liew D, Kwan P. Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurol. 2018 Mar 1;75(3):279-286. doi: 10.1001/jamaneurol.2017.3949. PubMed PMID: 29279892; PubMed Central PMCID: PMC5885858.
4)

Colic S, Wither RG, Lang M, Zhang L, Eubanks JH, Bardakjian BL. Prediction of antiepileptic drug treatment outcomes using machine learning. J Neural Eng. 2017 Feb;14(1):016002. doi: 10.1088/1741-2560/14/1/016002. Epub 2016 Nov 30. PubMed PMID: 27900948.