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.

Events Update

2018


May


Global Spine Congress 2018

May 2, 2018 — May 5, 2018

Singapore

Website: http://www.gsc2018.org


26th Biennial Congress of the European Society for Pediatric Neurosurgery

May 6, 2018 — May 9, 2018

Bonn, Germany

More Information


34th Annual Meeting Cervical Spine Research Society – Europe

May 9, 2018 — May 11, 2018

Lisbon, Portugal

More Information


45th ISSLS Annual Meeting

May 14, 2018 — May 18, 2018

Banff, Canada

Annual meeting of The International Society for the Study of the Lumbar Spine.

Website: http://www.issls.org


Israeli National Neurosurgical Society Annual Meeting

May 16, 2018 — May 18, 2018

Galilee, Israel

More Information


SENEC 2018

May 16, 2018 — May 18, 2018

Toledo, Spain

22nd Congress of the SENEC.

Contact: secretaria@senec.es


ESOC 2018 – 4th European Stroke Organisation Conference

May 16, 2018 — May 18, 2018

Gothenburg, Sweden

More Information


White Matter Dissection, Lectures + Hands-On Cadaver Course

May 23, 2018 — May 24, 2018

Graz, Austria

More Information


aStroke Meeting Puglia 2018

May 24, 2018 — May 25, 2018

San Giovanni Rotondo, Italy

More Information


Surgery Follows Function

May 25, 2018 — May 25, 2018

Graz, Austria

More Information


WFNS Neurosurgical Anatomy Committee 2018: 3D Cinema Lectures – Advanced Management of Vascular and Brain Tumors
26 May 2018
 http://bit.ly/wfns2018
 Announcement 

June

69. Jahrestagung der DGNC / 69th Annual Meeting of the DGNC

03.06.2018  06.06.2018
Münster, Germany
http://www.dgnc-kongress.de  

15th Interdisciplinary Cerebrovascular Symposium

Magdeburg, Germany

More Information


Microscopic and Endoscopic Approaches to the Skull Base

6 – 7 June 2018

 https://www.ircad.fr/training-center/course-calendar/?type=advanced&spec=neuro

 Brochure 


9th European Japanese Cerebrovascular Congress (EJCVC)

June 7, 2018

Milan, Italy

More Information


2nd Congress of Mediterranean Association of Neurological Surgeons (MANS 2018)
19 – 20 June 2018
 http://www.mans2018.it
 Scientific Program 
 Brochure 

Endoscopy in Neurosurgery: the advanced three-day course

June 20, 2018 — June 22, 2018

London, UK

More Information

ICRAN 2018
20 – 22 June 2018
 http://www.icran2018.it/
 Flyer 

13th European Low Grade Glioma Network

June 22, 2018 — June 23, 2018

Lisbon, Portugal

More Information


 

Hydrocephalus Forum 2018

21.06.2018  23.06.2017
Potsdam, Germany

https://www.hydrocephalusforum.de/hydrocephalus-forum/


EANS Lyon Hands-On Course

June 25, 2018 — June 29, 2018

Lyon, France

More Information


July


Seventh Annual World Course in Advanced Brain Tumour Surgery

July 12, 2018 — July 15, 2018

London, UK

More Information


CAANS 2018 Congress

24 – 27 July 2018

 http://www.caanscongress.info/

 Announcement 


 

August

INTS 2018

August 11, 2018 — August 16, 2018

Toronto, Canada

More Information

WFNS Symposium 2018

15TH – 19TH
AUGUST 2018

Hilton Kuala Lumpur,
Malaysia

http://wfns-symposia2018.com/


Prague Neurosurgical Week

August 29, 2018 — September 3, 2018

More Information


September

EUROSPINE 2018

September 19, 2018 — September 21, 2018

Barcelona, Spain

For more information please visit http://www.eurospinemeeting.org/f130000847.html

October


Spine in XXI Century

October 4, 2018 — October 8, 2018

Nis, Serbia

Association of Neurosurgeons of Russia
Russian Association of Spinal Surgeons
Serbian Neurosurgical Society

4th Meeting of the Serbian Neurosurgical Society
Joint Meeting with the Souteast Europe Neurosurgical Society

First announcement.


CNS Annual Meeting

October 6, 2018 — October 10, 2018

Chicago, IL, USA


13th EANO Meeting

October 9, 2018 — October 14, 2018

Stockholm, Sweden

Annual Meeting of the European Association of Neuro-oncology

Website.


Surgical anatomy of the arm in relation to nerve injuries

October 11, 2018 — October 12, 2018

Leiden, The Netherlands

More Information


EANS 2018

October 21, 2018 — October 25, 2018

Brussels, Belgium

More Information


4th European Congress of NeuroRehabilitation (ECNR) 2017

October 25, 2018 — October 28, 2018

Lausanne, Switzerland

More Information


ANTC 2017 – AIIMS NEUROTRAUMA CONFERENCE

October 27 — October 29

New Delhi, India

Taking place at the All India Institute of Medical Sciences.

Flyer.

November


Joint Global Neurofibromatosis Conference

November 2, 2018 — November 6, 2018

Paris, France

More Information


SNO 2018

November 15, 2018 — November 18, 2018

New Orleans, LA, USA

Society for Neuro-Oncology (SNO) Annual Meeting 2018

Website.

2019


January


2nd International Conference on Complications in Neurosurgery

January 25, 2019 — January 27, 2019

Mumbai, India

More Information


April


87th AANS Annual Scientific Meeting

April 13, 2019 — April 17, 2019

San Diego, CA, USA


September


EANS2019

September 24, 2019 — September 28, 2019

Dublin, Ireland

More Information


WFNS 2019 Interim Meeting

(9/9/2019 – 12/9/2019) / Beijing, China

http://www.wfns2019.org/index/


October


EUROSPINE 2019

October 16, 2019 — October 18, 2019

Helsinki, Finland

Please click HERE for more information.


CNS Annual Meeting

October 19, 2019 — October 23, 2019

San Francisco, CA, USA


SNO 2019

November 20, 2018 — November 24, 2018

Phoenix, AZ, USA

Society for Neuro-Oncology (SNO) Annual Meeting 2019

Website.

Why Me?: My 8-year treatment journey For Hemifacial Spasm (tic convulsif)

Why Me?: My 8-year treatment journey For Hemifacial Spasm (tic convulsif)

List Price : $4.99

ADD TO SHOPPING CART

Hemifacial spasm is a neuromuscular movement disorder characterized by brief or persistent involuntary contractions of the muscles innervated by the facial nerve. Its prevalence has been estimated at 11 cases per 100,000 individuals.

Hemifacial spasm is usually caused by an artery compressing the facial nerve at the root exit zone of the brainstem. As for treatment, many  patients obtain moderate or marked relief from local injections of botulinum toxin (Botox), which must be repeated every 3 to 4 months. Alternatively, microvascular decompression has a success rate of about 85%.

My story follows my more than 8 year struggle with this condition and is written to hopefully help those who are going through the same thing to a positive and successful treatment.

 

Handbook of Pediatric Neurosurgery

Handbook of Pediatric Neurosurgery 1st Edition

by George I. Jallo (Editor), Karl Kothbauer (Editor), Violette Recinos (Editor)

List Price: $124.99

ADD TO SHOPPING CART

Pediatric neurosurgery has witnessed considerable technological advances, resulting in more efficacious outcomes for young patients with hydrocephalus, epilepsy, brain tumors, spinal deformities, and a host of other conditions. The art of pediatric neurosurgery is a delicate balancing act—taking into account child and parents and emotional and disease challenges. As such, the management of serious neurological conditions in pediatric patients must encompass the big picture in addition to treating underlying pathologies.

Handbook of Pediatric Neurosurgery by George Jallo, Karl Kothbauer, and Violette Recinos covers the full depth and breadth of this uniquely rewarding subspecialty including congenital, developmental, and acquired disorders. The latest information is provided on anatomy, radiological imaging, and principles guiding the surgical and nonsurgical management of a full spectrum of neurological pathologies impacting infants and children. The book is divided into 11 sections and 56 chapters with state-of-the-art procedures, best practices, and clinical pearls from top pediatric neurosurgeons.

Key Features

Cranial disorders including Chiari malformations, encephaloceles, Dandy-Walker malformation, and craniosynostosis
Benign and malignant tumors—from the hypothalamus and optic pathways to the brainstem and spinal column
Spinal abnormalities such as spina bifida, tethered cord, and scoliosis
Clinical questions and answers at the end of chapters—ideal for self-testing and exam prep
Comprehensive and compact, this is the perfect backpack reference for neurosurgery residents and pediatric neurosurgery fellows to carry on rounds. It is also a must-have resource for seasoned pediatric neurosurgeons and all practitioners entrusted with the neurological care of pediatric patients.

Update: Anterior cervical discectomy and fusion complications

Anterior cervical discectomy and fusion complications

A 2-page survey was distributed to attendees at the 2015 Cervical Spine Research Society (CSRS) meeting. Respondents were asked to categorize 18 anterior cervical discectomy and fusion-related adverse events as either: “common and acceptable,” “uncommon and acceptable,” “uncommon and sometimes acceptable,” or “uncommon and unacceptable.” Results were compiled to generate the relative frequency of these responses for each complication. Responses for each complication event were also compared between respondents based on practice location (US vs. non-US), primary specialty (orthopedics vs. neurosurgery) and years in practice.

Of 150 surveys distributed, 115 responses were received (76.7% response rate), with the majority of respondents found to be US-based (71.3%) orthopedic surgeons (82.6%). Wrong level surgery, esophageal injury, retained drain, and spinal cord injury were considered by most to be unacceptable and uncommon complications. Dysphagia and adjacent segment disease occurred most often, but were deemed acceptable complications. Although surgeon experience and primary specialty had little impact on responses, practice location was found to significantly influence responses for 12 of 18 complications, with non-US surgeons found to categorize events more toward the uncommon and unacceptable end of the spectrum as compared with US surgeons.

These results serve to aid communication and transparency within the field of spine surgery, and will help to inform future quality improvement and best practice initiatives 1).

Vocal cord palsy

Cervical adjacent segment disease

Hoarseness

Hoarseness, approximately in 5% 2).

Dysphagia

Soft tissue damage due to the use of automatic retractors in MACDF is not minor and leads to general discomfort in the patient in spite of good neurological results. These problems most often occur when automatic retractors are used continuously for more than 1 hour, as well as when they are used in multiple levels. Dysphagia, dysphonia and local pain decreased with the use of transient manual blades for retraction, and with intermittent release following minimally invasive principles 3).

Postoperative dysphagia is a significant concern.

Dexamethasone, although potentially protective against perioperative dysphagia and airway compromise, could inhibit fusion, a generally proinflammatory process.

Postoperative hemorrhage

Cerebrospinal fluid (CSF) leaks

Cerebrospinal fluid (CSF) leaks, although uncommon, may occur and can be a potentially serious complication. Little is known regarding the fusion rate after durotomy in ACDF.

In a single-institution retrospective review, 14 patients who experienced CSF leak after ACDF between 1995 and September 2014 were identified.

The median follow-up was 13.1 months. The diagnoses included spondylosis/degenerative disc disease (n = 10), disc herniation with radiculopathy (n = 3), and kyphotic deformity (n = 1). Of ACDFs, 7 were 1-level, 5 were 2-level, and 2 were 3-level procedures. The posterior longitudinal ligament was intentionally opened in all cases, and the microscope was used in 9 cases. Durotomy was discovered intraoperatively in all cases and was generally repaired with a combination of fibrin glue and synthetic dural replacement. Lumbar drainage was used in 5 patients, and 3 patients reported orthostatic headaches, which resolved within 1 month. Two patients reported hoarseness, and 8 patients reported dysphagia; all cases were transient. Follow-up imaging for fusion assessment was available for 12 patients, and a 100% fusion rate was achieved with no postoperative infections.

ACDFs with CSF leak had a 100% fusion rate in this series, with generally excellent clinical outcomes, although it is difficult to conclude definitively that there is no effect on fusion rates because of the small sample size. However, given the relative rarity of this complication, this study provides important data in the clinical literature regarding outcomes after CSF leak in ACDFs 4).

Pharyngoesophageal perforation

Spinal subdural hematoma

A spinal subdural hematoma is a rare clinical entity with considerable consequences without prompt diagnosis and treatment. Throughout the literature, there are limited accounts of spinal subdural hematoma formation following spinal surgery. This report is the first to describe the formation of a spinal subdural hematoma in the thoracic spine following surgery at the cervical level. A 53-year-old woman developed significant paraparesis several hours after anterior cervical discectomy and fusion of C5-6. Expeditious return to operating room for anterior cervical revision decompression was performed, and the epidural hematoma was evacuated without difficulty. Postoperative imaging demonstrated a subdural hematoma confined to the thoracic level, and the patient was returned to the operating room for a third surgical procedure. Decompression of T1-3, with evacuation of the subdural hematoma was performed. Postprocedure, the patient’s sensory and motor deficits were restored, and, with rehabilitation, the patient gained functional mobility. Spinal subdural hematomas should be considered as a rare but potential complication of cervical discectomy and fusion. With early diagnosis and treatment, favorable outcomes may be achieved 5).

Carotid artery compression

Legatt et al., report herein a case of anterior cervical discectomy and fusion (ACDF) surgery in which findings on somatosensory evoked potential(SSEP) monitoring led to the correction of carotid artery compression in a patient with a vascularly isolated hemisphere (no significant collateral blood vessels to the carotid artery territory). The amplitude of the cortical SSEP component to left ulnar nerve stimulation progressively decreased in multiple runs, but there were no changes in the cervicomedullary SSEP component to the same stimulus. When the lateral (right-sided) retractor was removed, the cortical SSEP component returned to baseline. The retraction was then intermittently relaxed during the rest of the operation, and the patient suffered no neurological morbidity. Magnetic resonance angiography demonstrated a vascularly isolated right hemisphere. During anterior cervical spine surgery, carotid artery compression by the retractor can cause hemispheric ischemia and infarction in patients with inadequate collateral circulation. The primary purpose of SSEP monitoring during ACDF surgery is to detect compromise of the dorsal column somatosensory pathways within the cervical spinal cord, but intraoperative SSEP monitoring can also detect hemispheric ischemia. Concurrent recording of cervicomedullary SSEPs can help differentiate cortical SSEP changes due to hemispheric ischemia from those due to compromise of the dorsal column pathways. If there are adverse changes in the cortical SSEPs but no changes in the cervicomedullary SSEPs, the possibility of hemispheric ischemia due to carotid artery compression by the retractor should be considered 6).

Heterotopic Ossification

Heterotopic ossification (HO) has been reported following total hip, knee, cervical arthroplasty, and lumbar arthroplasty, as well as following posterolateral lumbar fusion using recombinant human morphogenetic protein 2 (rhBMP-2). Data regarding HO following anterior cervical discectomy and fusion (ACDF) with rhBMP-2 are sparse. A subanalysis was done of the prospective, multicenter, investigational device exemption trial that compared rhBMP-2 on an absorbable collagen sponge (ACS) versus allograft in ACDF for patients with symptomatic single-level cervical degenerative disc disease.

To assess differences in types of HO observed in the treatment groups and effects of HO on functional and efficacy outcomes, clinical outcomes from previous disc replacement studies were compared between patients who received rhBMP-2/ACS versus allograft. Rate, location, grade, and size of ossifications were assessed preoperatively and at 24 months, and correlated with clinical outcomes. RESULTS Heterotopic ossification was primarily anterior in both groups. Preoperatively in both groups, and including osteophytes in the target regions, HO rates were high at 40.9% and 36.9% for the rhBMP-2/ACS and allograft groups, respectively (p = 0.350). At 24 months, the rate of HO in the rhBMP-2/ACS group was higher than in the allograft group (78.6% vs 59.2%, respectively; p < 0.001). At 24 months, the rate of superior-anterior adjacent-level Park Grade 3 HO was 4.2% in both groups, whereas the rate of Park Grade 2 HO was 19.0% in the rhBMP-2/ACS group compared with 9.8% in the allograft group. At 24 months, the rate of inferior-anterior adjacent-level Park Grade 2/3 HO was 11.9% in the rhBMP-2/ACS group compared with 5.9% in the allograft group. At 24 months, HO rates at the target implant level were similar (p = 0.963). At 24 months, the mean length and anteroposterior diameter of HO were significantly greater in the rhBMP-2/ACS group compared with the allograft group (p = 0.033 and 0.012, respectively). Regarding clinical correlation, at 24 months in both groups, Park Grade 3 HO at superior adjacent-level disc spaces significantly reduced range of motion, more so in the rhBMP-2/ACS group. At 24 months, HO negatively affected Neck Disability Index scores (excluding neck/arm pain scores), neurological status, and overall success in patients in the rhBMP-2/ACS group, but not in patients in the allograft group.

Implantation of rhBMP-2/ACS at 1.5 mg/ml with polyetheretherketone spacer and titanium plate is effective in inducing fusion and improving pain and function in patients undergoing ACDF for symptomatic single-level cervical degenerative disc disease. At 24 months, the rate and dimensions (length and anteroposterior diameter) of HO were higher in the rhBMP-2/ACS group. At 24 months, range of motion was reduced, with Park Grade 3 HO in both treatment groups. The impact of Park Grades 2 and 3 HO on Neck Disability Index success, neurological status, and overall success was not consistent among the treatment groups. The study data may offer a deeper understanding of HO after ACDF and may pave the way for improved device designs 7).

Subsidence

There is evidence documenting relatively frequent complications in stand-alone cage assisted ACDF, such as cage subsidence and cervical kyphosis 8).

Subsidence irrespective of the measurement technique or definition does not appear to have an impact on successful fusion and/or clinical outcomes. A validated definition and standard measurement technique for subsidence is needed to determine the actual incidence of subsidence and its impact on radiographic and clinical outcomes 9).


The results of a observational study were in accordance with those of the published randomized controlled trials (RCTs), suggesting substantial pain reduction both after anterior cervical interbody fusion (AIF) and Cervical total disc replacement, with slightly greater benefit after arthroplasty. The analysis of atypical patients suggested that, in patients outside the spectrum of clinical trials, both surgical interventions appeared to work to a similar extent to that shown for the cohort in the matched study. Also, in the longer-term perspective, both therapies resulted in similar benefits to the patients 10).

Case series

Analysis of 1000 consecutive patients undergoing Anterior cervical discectomy and fusion (ACDF) in an outpatient setting demonstrated surgical complications occur at a low rate (<1%) and can be appropriately diagnosed and managed in 4-hour ASC PACU window. Comparison with inpatient ACDF surgery cohort demonstrated similar results, highlighting that ACDF can be safely performed in an outpatient ambulatory surgery setting without compromising surgical safety. To decrease cost of care, surgeons can safely consider performing 1- and 2-level ACDF in an ASC environment 11).


A retrospective case series of 37 patients, paying special attention to immediate complications related to the use of mechanical retraction of soft tissue (dysphagia, dysphonia, esophageal lesions and local hematoma); and a comparative analysis of the outcomes after changes in the retraction method.

All selected cases had a positive neurological symptom response in relation to neuropathic pain. Dysphagia and dysphonia were found during the first 72 h in 94.1% of the cases in which automatic mechanical retraction was used for more than one hour during the surgical procedure. A radical change was noted in the reduction of the symptoms after the use of only manual protective blades without automatic mechanical retraction: 5.1% dysphagia and 0% dysphonia in the immediate post-operative period, P = 0.001.

Soft tissue damage due to the use of automatic retractors in MACDF is not minor and leads to general discomfort in the patient in spite of good neurological results. These problems most often occur when automatic retractors are used continuously for more than 1 hour, as well as when they are used in multiple levels. Dysphagia, dysphonia and local pain decreased with the use of transient manual blades for retraction, and with intermittent release following minimally invasive principles 12).

1)

Wilson JR, Radcliff K, Schroeder G, Booth M, Lucasti C, Fehlings M, Ahmad N, Vaccaro A, Arnold P, Sciubba D, Ching A, Smith J, Shaffrey C, Singh K, Darden B, Daffner S, Cheng I, Ghogawala Z, Ludwig S, Buchowski J, Brodke D, Wang J, Lehman RA, Hilibrand A, Yoon T, Grauer J, Dailey A, Steinmetz M, Harrop JS. Frequency and Acceptability of Adverse Events After Anterior Cervical Discectomy and Fusion: A Survey Study From the Cervical Spine Research Society. Clin Spine Surg. 2018 Apr 27. doi: 10.1097/BSD.0000000000000645. [Epub ahead of print] PubMed PMID: 29708891.
2)

Morpeth JF, Williams MF. Vocal fold paralysis after anterior cervical diskectomy and fusion. Laryngoscope. 2000 Jan;110(1):43-6. PubMed PMID: 10646714.
3) , 12)

Ramos-Zúñiga R, Díaz-Guzmán LR, Velasquez S, Macías-Ornelas AM, Rodríguez-Vázquez M. A microsurgical anterior cervical approach and the immediate impact of mechanical retractors: A case control study. J Neurosci Rural Pract. 2015 Jul-Sep;6(3):315-9. doi: 10.4103/0976-3147.158748. PubMed PMID: 26167011; PubMed Central PMCID: PMC4481782.
4)

Elder BD, Theodros D, Sankey EW, Bydon M, Goodwin CR, Wolinsky JP, Sciubba DM, Gokaslan ZL, Bydon A, Witham TF. Management of Cerebrospinal Fluid Leakage During Anterior Cervical Discectomy and Fusion and Its Effect on Spinal Fusion. World Neurosurg. 2015 Nov 30. pii: S1878-8750(15)01588-0. doi: 10.1016/j.wneu.2015.11.033. [Epub ahead of print] PubMed PMID: 26654925.
5)

Protzman NM, Kapun J, Wagener C. Thoracic spinal subdural hematoma complicating anterior cervical discectomy and fusion: case report. J Neurosurg Spine. 2015 Oct 13:1-5. [Epub ahead of print] PubMed PMID: 26460756.
6)

Legatt AD, Laarakker AS, Nakhla JP, Nasser R, Altschul DJ. Somatosensory evoked potential monitoring detection of carotid compression during ACDF surgery in a patient with a vascularly isolated hemisphere. J Neurosurg Spine. 2016 Nov;25(5):566-571. PubMed PMID: 27285667.
7)

Arnold PM, Anderson KK, Selim A, Dryer RF, Kenneth Burkus J. Heterotopic ossification following single-level anterior cervical discectomy and fusion: results from the prospective, multicenter, historically controlled trial comparing allograft to an optimized dose of rhBMP-2. J Neurosurg Spine. 2016 Sep;25(3):292-302. doi: 10.3171/2016.1.SPINE15798. Epub 2016 Apr 29. PubMed PMID: 27129045.
8)

Cloward RB: The anterior approach for removal of ruptured cervical disks. 1958. J Neurosurg Spine 6:496-511, 2007
9)

Karikari IO, Jain D, Owens TR, Gottfried O, Hodges TR, Nimjee SM, Bagley CA. Impact of Subsidence on Clinical Outcomes and Radiographic Fusion Rates in Anterior Cervical Discectomy and Fusion: A Systematic Review. J Spinal Disord Tech. 2014 Feb;27(1):1-10. PubMed PMID: 24441059.
10)

Staub LP, Ryser C, Röder C, Mannion AF, Jarvik JG, Aebi M, Aghayev E. Total disc arthroplasty versus anterior cervical interbody fusion: use of the spine tango registry to supplement the evidence from RCTs. Spine J. 2015 Dec 7. pii: S1529-9430(15)01763-5. doi: 10.1016/j.spinee.2015.11.056. [Epub ahead of print] PubMed PMID: 26674445.
11)

McGirt MJ, Mehrlich M, Parker SL, Asher AL, Adamson TE. 165 ACDF in the Outpatient Ambulatory Surgery Setting: Analysis of 1000 Consecutive Cases and Comparison to Hospital Inpatient ACDF. Neurosurgery. 2015 Aug;62 Suppl 1:220. doi: 10.1227/01.neu.0000467129.12773.a3. PubMed PMID: 26182011.

Invasive meningioma

Invasive meningioma

Invasive intracranial meningioma is a common neoplasm of central nervous system, which can infiltrate adjacent tissues (dura materarachnoid membrane, vascular space and skull) without atypical hyperplasia 1) 2)

In general, the pathological nature of meningioma determines its association with the brain parenchyma, which is that benign meningioma is usually compressive to the brain parenchyma due to its expansive growth, and malignant meningioma is invasive into the neighboring brain parenchyma due to its intrusive growth 3) 4). However, clinical observations have indicated that there is a sub-group of benign meningioma displaying a malignant growth pattern, that is, invasion into the neighboring brain tissue 5) 6) 7) 8) 9).

According to the experience gained in 19 cases, it was observed that there were certain features shared by these invasive benign meningiomas. The peak age of onset was ~50 years; the main manifestation was mild focal neurological deficits, which included dysphasia, and decreased sensation and muscle power of the contralateral limb. The MRI findings usually had the following characteristics: The lesions were located at the convexity of the cerebral hemisphere involving the central lobe, with an extensive base at the dural matter and evident ‘tail sign’; there was a minimal boundary between the tumor and the neighboring brain cortex; finally, and probably most importantly, the apex of tumor often enwrapped the normal brain tissue and associated vessels.

Due to the malignant growth, it was challenging to completely remove this benign meningioma while ensuring that neurological function remained intact. Resection of the earliest 4 cases was performed according to the traditional extra-capsular strategy, which was to coagulate and divide the tumor base first, and then continue the dissection along the interface between the tumor and brain parenchyma. This approach inevitably damaged the vessels transiting from and into the tumor. The observation that all 4 cases had permanent neurological deficits confirmed the disadvantage associated with this surgical strategy. Following careful analysis of the surgical outcomes, the resection method was modified by combining intra- and extra-capsular approaches. The first step was the same as the classical method, which was to coagulate and divide the tumor base. Afterwards, intra-capsular extirpation of the central part of the tumor was performed. Care was taken not to damage the transit vessels when approaching the tumor-brain interface. The enucleation of the central part of the tumor created a working space, which greatly facilitated the identification of the transit vessels. After this, the tumor was separated from brain parenchyma along the sub-arachnoid membrane. The use of a sponge during this dissection process was important. Finally, it was critical to separate the enwrapped brain cortex and associated vessels from the invading ‘cauliflower-like’ nodules of the meningioma. It is recommended that no efforts are spared in this process, since the enwrapped brain tissue may have retained its ability to function. The observation that there was only 1 case with mild neurological impairment post-operatively in the later 15 cases confirms the advantage of the modified strategy.

In summary, the present study further revealed the clinical features of the invasive benign meningioma and indicated the advantage of combined intra-extra capsular strategy for the surgical resection 10).


Identification of risk factors for perioperative epilepsy remains crucial in the care of patients with meningioma. Moreover, associations of brain invasion with clinical and radiological variables have been largely unexplored. Brain invasion was identified as a new and strong predictor for preoperative, but not postoperative, seizures. Although also associated with increased peritumoral edema, seizures in patients with invasive meningioma might be facilitated substantially by cortical invasion itself. Consideration of seizures in consultations between the neurosurgeon and neuropathologist can improve the microscopic detection of brain invasion 11).

Case series

2018

Hess et al., hypothesized that invasion of the cortex and subsequent increased edema facilitate seizures, and they compared radiological data and perioperative seizures in patients with brain-invasive meningioma or noninvasive meningioma.

Correlations of brain invasion with tumor and edema volumes and preoperative and postoperative seizures were analyzed in univariate and multivariate analyses.

Totals of 108 (61%) females and 68 (39%) males with a median age of 60 years and harboring totals of 92 (52%) grade I, 79 (45%) grade II, and 5 (3%) grade III tumors were included. Brain invasion was found in 38 (22%) patients and was absent in 138 (78%) patients. The tumors were located at the convexity in 72 (41%) patients, at the falx cerebri in 26 (15%), at the skull base in 69 (39%), in the posterior fossa in 7 (4%), and in the ventricle in 2 (1%); the median tumor and edema volumes were 13.73 cm3 (range 0.81-162.22 cm3) and 1.38 cm3 (range 0.00-355.80 cm3), respectively. As expected, edema volume increased with rising tumor volume (p < 0.001). Brain invasion was independent of tumor volume (p = 0.176) but strongly correlated with edema volume (p < 0.001). The mean edema volume in noninvasive tumors was 33.0 cm3, but in invasive tumors, it was 130.7 cm3 (p = 0.008). The frequency of preoperative seizures was independent of the patients’ age, sex, and tumor location; however, the frequency was 32% (n = 12) in patients with invasive meningioma and 15% (n = 21) in those with noninvasive meningioma (p = 0.033). In contrast, the probability of detecting brain invasion microscopically was increased more than 2-fold in patients with a history of preoperative seizures (OR 2.57, 95% CI 1.13-5.88; p = 0.025). In univariate analyses, the rate of preoperative seizures correlated slightly with tumor volume (p = 0.049) but strongly with edema volume (p = 0.014), whereas seizure semiology was found to be independent of brain invasion (p = 0.211). In multivariate analyses adjusted for age, sex, tumor location, tumor and edema volumes, and WHO grade, rising tumor volume (OR 1.02, 95% CI 1.00-1.03; p = 0.042) and especially brain invasion (OR 5.26, 95% CI 1.52-18.15; p = 0.009) were identified as independent predictors of preoperative seizures. Nine (5%) patients developed new seizures within a median follow-up time of 15 months after surgery. Development of postoperative epilepsy was independent of all clinical variables, including Simpson grade (p = 0.133), tumor location (p = 0.936), brain invasion (p = 0.408), and preoperative edema volume (p = 0.081), but was correlated with increasing preoperative tumor volume (p = 0.004). Postoperative seizure-free rates were similar among patients with invasive and those with noninvasive meningioma (p = 0.372).

Brain invasion was identified as a new and strong predictor for preoperative, but not postoperative, seizures. Although also associated with increased peritumoral edema, seizures in patients with invasive meningioma might be facilitated substantially by cortical invasion itself. Consideration of seizures in consultations between the neurosurgeon and neuropathologist can improve the microscopic detection of brain invasion12).

2017

From February 2014 to February 2016, 59 patients with invasive meningioma were enrolled in a study. Invasive meningioma was confirmed in all patients by operation. Information about clinical manifestations, pathological features, preoperative imaging and surgical treatment were collected and analyzed. After surgery, pathological specimens were collected, and cases were confirmed as invasive meningioma by pathological examination. The course of disease ranged from 15 days to 7 years (average, 13.2 months). We used World Health Organization (WHO) criteria for classification of meningioma in the nervous system tumors as our reference. Symptoms were as follows: Intracranial hypertension (29 cases), cranial nerve dysfunction (10 cases), epilepsy (11 cases) and other symptoms (9 cases). We had 56 cases of WHO grade I; 6 cases of WHO grade II and 7 cases of WHO grade III. Surgical removal was: Simpson grade I (56 cases), Simpson grade II (2 cases), Simpson grade III and above (56 cases). We used before surgery imaging data to formulate our surgical plan. In general, during surgeries we did not proceed to complete resection, because in the majority of cases, some key structures were invaded and meningioma was very deep and any attempt for total resection could easily lead to significant damage to these structures 13).

1995

A study was undertaken to investigate the correlation between histological invasiveness and proliferating potential and clinical recurrence in meningioma. In 39 meningiomas, the histological findings at the tumour-brain interface zone were classified into 3 types, consisting of 29 cases of non-invasion (NON). 7 cases of nodular invasion (NOD), and 3 cases of intermingled invasion (INT). Proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer region (AgNOR) indices were studied. PCNA indices (mean +/- standard error) of NON, NOD. and INT were 1.7 +/- 0.1%, 5.2 +/- 0.5%, and 7.5 +/- 0.7%. respectively, and the AgNOR indices (dot number/nucleus) were 1.50 +/- 0.03, 2.00 +/- 0.04, and 2.22 +/- 0.07, respectively. Significant differences were found among the three types in both parameters. Clinically, tumour recurrence was observed in 1/29 NON, 4/7 NOD, and 2/2 INT cases, indicating a higher incidence of recurrence in invasive meningiomas (NOD plus INT). Four of 32 patients who underwent gross total removal of the tumours showed recurrence, and all of these four tumours were invasive meningiomas. The results of the present study showed that tumour invasiveness as measured by PCNA + AgNOR indices correlated well with high proliferative potential and clinical recurrence 14).

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