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Garjan TG, Sharifzadeh M, Khodagholi F, Musavi SM, Hasanzadeh G, Zarindast M, Gorji A. A novel traumatic brain injury model for induction of mild brain injury in rats. J Neurosci Methods. 2014 Jun 3. pii: S0165-0270(14)00203-9. doi: 10.1016/j.jneumeth.2014.05.035. [Epub ahead of print] PubMed PMID: 24906055.

McHugh BJ, Baranoski JF, Malhotra A, Vortmeyer AO, Sze G, Duncan CC. Intracranial infantile hemangiopericytoma. J Neurosurg Pediatr. 2014 Jun 6:1-6. [Epub ahead of print] PubMed PMID: 24905842.

Hervey-Jumper SL, Garton HJ, Lau D, Altshuler D, Quint DJ, Robertson PL, Muraszko KM, Maher CO. Differences in vascular endothelial growth factor receptor expression and correlation with the degree of enhancement in medulloblastoma. J Neurosurg Pediatr. 2014 Jun 6:1-8. [Epub ahead of print] PubMed PMID: 24905841.

Journal of Neurosurgery Junio 2014

Suprasellar meningioma


Endoscopic endonasal surgery for suprasellar meningiomas: experience with 75 patients

With the goal of gross-total tumor resection and visual improvement, endoscopic endonasal surgery (EES) can achieve very good results, (comparable to microscopic approaches) for the treatment of suprasellar meningiomas. Avoidance of brain and optic nerve retraction, preservation of the vascularization of the optic apparatus, and wide decompression of the optic canals are the main advantages of EES for the treatment of suprasellar meningiomas, while cerebrospinal fluid leakage remain a disadvantage 1).

1) Koutourousiou M, Fernandez-Miranda JC, Stefko ST, Wang EW, Snyderman CH, Gardner PA. Endoscopic endonasal surgery for suprasellar meningiomas: experience with 75 patients. J Neurosurg. 2014 Jun;120(6):1326-39. doi: 10.3171/2014.2.JNS13767. Epub 2014 Mar 28. PubMed PMID: 24678782.

Mary Koutourousiou, MD, joined the University of Pittsburgh Department of Neurological Surgery in May 2012 to complete a clinical fellowship in open and endoscopic endonasal skull base surgery with Drs. P.A. Gardner and J.C. Fernandez-Miranda. Prior to this appointment, since April 2010, she was a research fellow at the University of Pittsburgh Department of Neurological Surgery. Dr. Koutourousiou, a native from Thessaloniki, Greece, received her medical degree from the Aristotle University of Thessaloniki, Greece and completed her neurosurgical residency at the General Hospital of Athens “G. Gennimatas”, Athens, Greece. She has completed a clinical fellowship in minimally invasive and endoscopic neurosurgery with Prof. J.A. Grotenhuis at the Department of Neurosurgery, UMC St Radboud, Nijmegen, The Netherlands. Dr. Koutourousiou is accomplishing her Ph.D. on the Endocrinology and Pathophysiology of pituitary adenomas at the University of Athens, School of Medicine, Greece.

Update: Middle frontal gyrus approach


Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain

The operative approaches to the third ventricle are divided on the basis of whether they are suitable for reaching the anterior or posterior part of the 3rd ventricle. The approaches suitable for lesions within or compressing the anterior portion of the 3rd ventricle are the transsphenoidal approach, subfrontal approach, frontotemporal approach, subtemporal approach, anterior transcallosal approach, and anterior transventricular. The approaches suitable for reaching the posterior portion of the 3rd ventricle are the posterior transcallosal, posterior transventricular, occipital transtentorial approach, and infratentorial supracerebellar approach 1).

The transcortical middle frontal gyrus approach is an excellent route for the excision of tumors in the ipsilateral frontal horn of the lateral ventricle (LV), the anterior body of the lateral ventricle, and the anterior or superior third ventricle.

This is the approach most frequently used to excise tumors of the frontal horn. That most neurosurgeons are comfortable with passing a ventricular catheter into the frontal horn of the lateral ventricle probably accounts for the relative ease of this approach; it is simply an extension of that common neurosurgical maneuver. Tumors that extend inferiorly from the lateral ventricle into the third ventricle and require subchoroidal exposure for removal are better visualized when using a transcortical than a transcallosal approach 2).

The middle frontal gyrus is usually found 3.5 cm from the midline and 1 cm in front of the coronal suture. Its location can be confirmed with aid of image guidance. Image guidance can be helpful at this point for planning frontal transcortical access to the anterior third ventricle (foraminal entry).

A right-sided approach (nondominant hemisphere) is preferred unless the tumor’s position in the lateral ventricle dictates otherwise. A rectangular flap of approximately 6 x 4 cm, starting 2 cm behind the coronal suture and centered on the middle of the middle frontal gyrus, is made. Its medial limit is about 1 cm off the midline. Image guidance helps in planning the craniotomy

In the middle frontal gyrus approach, a 4 cm incision is made paralell to the axis of the middle frontal gyrus above and anterior to Broca’s area, and anterior to the motor strip 3). ; about the same point as used for frontal ventriculostomy. see Kocher’s point.

In cases of small ventricles or large tumors, a longer cortical incision prevents brain injury.

The approach is directed from the middle frontal gyrus toward the contralateral inner canthus in a plane extending from the coronal suture to the external auditory meatus. The dissection is done with blunt instruments. The lateral ventricle is usually entered near the foramen of Monro (FM).

A study compared the damage of main neural bundles between virtualtrans-F1 and trans-F2 corridors by means of diffusion tensor tractography method (DTT) in 11 magnetic resonance imaging (MRI) exams from clinical series (22 hemispheres, regardless of dominance). Corpus callosum, cingulum, subdivisions I and II of superior longitudinal fasciculus (SLF I and SLF II), corticoreticular as well as pyramidal tracts crossing both approaches were subjected to surgical violation. Both approaches served a similar total number of fibres (0.94 to 1.78 [× 103]).Trans-F1 route caused significantly greater damage of total white matter volume(F1: 8.26 vs. F2: 7.16 mL), percentage of SLF I fibres (F1: 78.6% vs. F2: 28.6%)and cingulum (F1: 49.4% vs. F2: 10.6%), whereas trans-F2 route interrupted morecorticoreticular fibres (F1: 4.5% vs. F2: 30.7%). Pyramidal tract (F1: 0.6% vs. F2:1.3%) and SLF II (F1: 15.9% vs. F2: 26.2%) were marginally more vulnerable incase of the access via middle frontal gyrus. Both approaches destroyed 7% of callosal fibres. Summarising the above DTT findings, trans-F2 route disrupted a greater number of fibres from eloquent neural bundles (SLF II, pyramidal and corticoreticular tracts), therefore is regarded as inferior to trans-F1 one. Due to lack of up-to-date guidelines with recommendations of the approaches to LV or FM, an individual preoperative planning based on DTT should precede a surgery 4).

1) , 3) Rhoton AL Jr, Yamamoto I, Peace DA. Microsurgery of the third ventricle: Part 2. Operative approaches. Neurosurgery. 1981 Mar;8(3):357-73. PubMed PMID: 7242884.
2) Rhoton AL Jr, Fujii K, Fradd B: Microsurgical anatomy of the anterior choroidal artery. Surg Neurol 12:171-187, 1979
4) Szmuda T, Słoniewski P, Szmuda M, Waszak PM, Starzyńska A. Quantification of white matter fibre pathways disruption in frontal transcortical approach to the lateral ventricle or the interventricular foramen in diffusion tensor tractography. Folia Morphol (Warsz). 2014 May;73(2):129-38. doi: 10.5603/FM.2013.0063. PubMed PMID: 24902089.

Top Read: Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial.

Lancet Neurol. 2014 May 15. pii: S1474-4422(14)70084-5. doi: 10.1016/S1474-4422(14)70084-5. [Epub ahead of print]

Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial.



The benefit of statins in patients with acute aneurysmal subarachnoid haemorrhage is unclear. We aimed to determine whether simvastatin 40 mg could improve the long-term outcome in patients with this disorder.


In this international, multicentre, randomised, double-blind trial, we enrolled patients aged 18-65 years with confirmatory evidence of an aneurysmal subarachnoid haemorrhage and presenting less than 96 h from ictus from 35 acute neurosurgical centres in nine countries. Patients were randomly allocated (1:1) to receive either simvastatin 40 mg or placebo once a day for up to 21 days. We used a computer-generated randomisation code to randomise patients in every centre by blocks of ten (five simvastatin, five placebo). Participants and investigators were masked to treatment assignment. The primary outcome was the distribution of modified Rankin Scale (mRS) score obtained by questionnaire at 6 months. Analyses were done on the intention-to-treat population. This trial has been completed and is registered with Current Controlled Trials, number ISRCTN75948817.


Between Jan 6, 2007, and Feb 1, 2013, apart from the period between May 15, 2009, and Feb 8, 2011, when recruitment was on hold, 803 patients were randomly assigned to receive either simvastatin 40 mg (n=391) or placebo (n=412). All patients were included in the intention-to-treat population. 782 (97%) patients had outcome data recorded at 6 months, of whom 560 (72%) were classed as having a favourable outcome, mRS 0-2 (271 patients in the simvastatin group vs 289 in the placebo group). The primary ordinal analysis of the mRS, adjusted for age and World Federation of Neurological Surgeons grade on admission, gave a common odds ratio (OR) of 0·97, 95% CI 0·75-1·25; p=0·803. At 6 months, we recorded 37 (10%) deaths in the simvastatin group compared with 35 (9%) in the placebo group (log-rank p=0·592). 70 (18%) serious adverse events were reported in the simvastatin group compared with 74 (18%) in the placebo group. No suspected unexpected serious adverse reactions were reported.


The STASH trial did not detect any benefit in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid haemorrhage. Despite demonstrating no safety concerns, we conclude that patients with subarachnoid haemorrhage should not be treated routinely with simvastatin during the acute stages.


British Heart Foundation.

Top Read: Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

Br J Cancer. 2014 May 27;110(11):2655-61. doi: 10.1038/bjc.2014.209. Epub 2014 May 1.

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.


Background:Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma.Methods:Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416).Results:The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6).Conclusions:Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings.

Top Read: Predictors of outcome after treatment of mild traumatic brain injury: a pilot study.

J Head Trauma Rehabil. 2014 Mar-Apr;29(2):109-16. doi: 10.1097/HTR.0b013e3182860506.

Predictors of outcome after treatment of mild traumatic brain injury: a pilot study.



To determine factors affecting outcome of comprehensive outpatient rehabilitation of individuals who sustained a mild traumatic brain injury.


From a 4-year series of referrals, 49 nonconsecutive participants met criteria for mild traumatic brain injury (ie, loss of consciousness <30 minutes, Glasgow Coma Scale score >12).


Outpatient, community-based postconcussion clinic at a rehabilitation hospital.


Participants and therapy staff completed the Mayo-Portland Adaptability Inventory-Fourth Edition (MPAI-4) at the initiation and conclusion of treatment. Participants were also administered the Trail Making Test at the start of treatment.


Participants generally gave poorer adaptability ratings than staff at the beginning and discharge of treatment. Regression analyses revealed that after controlling for baseline ratings, psychiatric history was associated with worse participant-rated MPAI-4 Adjustment scores at treatment discharge, whereas better Trail Making Test Part B performance at initiation of treatment predicted better participant-rated MPAI-4 Ability at treatment discharge.


Premorbid demographic and baseline neurocognitive factors should be taken into account prior to comprehensive treatment of mild traumatic brain injury, as they can influence long-term outcomes. Adaptability ratings from both staff and participants can be useful in gaining different perspectives and assessing factors affecting recovery.