Update: Antiplatelet reversal

Antiplatelet reversal

Antiplatelet therapy is common and complicates the operative management of acute intracranial hemorrhage. Little data exist to guide antiplatelet reversal strategies.

The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes.

Data assessing the relationship between outcome and prehospital antiplatelet agents in the setting of ICH is conflicting in both the trauma and the stroke literature. Only one retrospective review specifically addressed outcomes after attempted reversal with platelet transfusion. Further study is needed to determine whether platelet transfusion ameliorates hematoma enlargement and/or improves outcome in the setting of acute ICH 1).

Raimondi et al., recommend discontinuation of the antiplatelet, as well as administration of platelet transfusions and desmopressin only in the setting of life-threatening bleeding 2).


An online survey detailing antiplatelet reversal strategies in patients presenting with acute operative intracranial hemorrhage (subdural hematoma(SDH), epidural hematoma (EDH), and intracerebral hemorrhage (ICH) was distributed to board certified neurosurgeons in the North America.

Of the 2,782 functional email addresses, there were 493 (17.7%) responses to question #1 and 429 (15.4%) completed surveys. Most respondents chose to perform no additional laboratory testing prior to surgical intervention, regardless of hemorrhage type. The most common antiplatelet reversal strategy in the presence of aspirin was platelet transfusion (SDH and ICH) or no intervention (EDH). The most common antiplatelet reversal strategy in the presence of an Adenosine diphosphate receptor inhibitor or DAPT was platelet transfusion or platelet transfusion with DDAVP administration. There was a statistically significant difference in management strategy depending on the antiplatelet therapy (p < 0.001).

When patients on antiplatelet medication present with operative intracranial hemorrhage, the majority of neurosurgeons do not perform qualitative platelet function testing. Antiplatelet reversal strategies are significantly influenced by the antiplatelet therapy with more aggressive reversal strategies employed in the presence of ADP antagonist3).

References

1)

Campbell PG, Sen A, Yadla S, Jabbour P, Jallo J. Emergency reversal of antiplatelet agents in patients presenting with an intracranial hemorrhage: a clinical review. World Neurosurg. 2010 Aug-Sep;74(2-3):279-85. doi: 10.1016/j.wneu.2010.05.030. Review. PubMed PMID: 21492561.
2)

Raimondi P, Hylek EM, Aronis KN. Reversal Agents for Oral Antiplatelet and Anticoagulant Treatment During Bleeding Events: Current Strategies. Curr Pharm Des. 2017;23(9):1406-1423. doi: 10.2174/1381612822666161205110843. Review. PubMed PMID: 27917717.
3)

Foreman PM, Ilyas A, Mooney J, Schmalz PGR, Walters BC, Griessenauer CJ. Antiplatelet Medication Reversal Strategies in Operative Intracranial Hemorrhage: A Survey of Practicing Neurosurgeons. World Neurosurg. 2018 May 18. pii: S1878-8750(18)31017-9. doi: 10.1016/j.wneu.2018.05.064. [Epub ahead of print] PubMed PMID: 29783009.

Update: Mastoid emissary vein

Mastoid emissary vein

The mastoid emissary vein drains superolaterally into the sigmoid sinus.

For a craniotomy if the asterion 1), is not easily identified place the burr hole over the mastoidemissary vein.

It is especially important from the neurosurgical point of view, because it is located in variable number in the area of the occipitomastoid suture and it can become a source of significant bleeding in surgical approaches through the mastoid process, especially in retrosigmoid craniotomy, which is used for approaches to pathologies localized in the cerebellopontine angle.

Kim et al., conducted a study on 106 cadaveric dry skull specimens looking at the incidence, position and caliber of mastoid emissary foramina. 83.7% of skulls were found to have at least one foramen with a mean diameter of 1.64 mm and the largest specimen measuring 7 mm 2).

Ideal imaging method for diagnosis of these neglected structures when planning a surgical approach is high-resolution computed tomography.


Hampl et al., studied a group of 295 skulls obtained from collections of five anatomy departments and the National Museum of the Czech Republic. Both quantitative and qualitative parameters of the mastoid foramen were evaluated depending on side of appearance and gender. Individual distances of the mastoid foramen from clearly defined surface landmarks (asterion, apex of mastoid process, foramen magnum) and other anatomical structures closely related to this issue (width of groove for sigmoid sinus, diameters of internal and external openings of mastoid foramen) were statistically processed.

The most frequently represented type of the mastoid foramen is type II by Louis (41.2%). The differences between right and left sides were not statistically significant. In men there was a higher number of openings on the right side and in qualitative parameters the type III and IV predominated, whereas in women the types I and II were more frequent. In men, greater distances from the mastoid foramen were observed when evaluating qualitative parameters for defined surface landmarks. Mean size of the external opening diameter was 1.3 mm; however, several openings measured up to 7 mm 3).

1)

Day JD, Tschabitscher M. Anatomic position of the asterion. Neurosurgery. 1998 Jan;42(1):198-9. PubMed PMID: 9442525.
2)

Kim LK, Ahn CS, Fernandes AE. Mastoid emissary vein: anatomy and clinical relevance in plastic & reconstructive surgery. J Plast Reconstr Aesthet Surg. 2014 Jun;67(6):775-80. doi: 10.1016/j.bjps.2014.03.002. Epub 2014 Mar 21. PubMed PMID: 24713148.
3)

Hampl M, Kachlik D, Kikalova K, Riemer R, Halaj M, Novak V, Stejskal P, Vaverka M, Hrabalek L, Krahulik D, Nanka O. Mastoid foramen, mastoid emissary vein and clinical implications in neurosurgery. Acta Neurochir (Wien). 2018 May 20. doi: 10.1007/s00701-018-3564-2. [Epub ahead of print] PubMed PMID: 29779186.

Update: Selenium and glioma

Selenium and glioma

Reliable supply of selenium is important since selenium compounds can affect tumor microenvironment and neoangiogenesis in malignant gliomas via induction of apoptosis and alteration of matrix metalloproteinases expression.

In 1990 Philipov and Tzatchev added selenium tablets to the diet of 15 patients with malignant brain tumors. In twelve patients with glioblastoma multiforme this treatment didn’t prolong the postoperative survival 1).


Yakubov et al. summarized findings focusing on the anti-toxicity and cancer-preventive properties of selenium and their implication in current multimodal therapies including temozolomide (Temodal), cyclophosphamide (Endoxan), and cisplatin (DDP, Platiblastin, and Platinol).

They sheded light on unintended side effects in chemotherapy and the developments of novel combinatorial chemotherapeutics with selenium compounds. They found that selenium and selenium compounds have dual action profiles with direct anti-cancer and chemotherapy-intensifier effects as well as neuroprotective and cytoprotective agents 2).


Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was detected in vitro, accompanied by PARP cleavage, caspases activation and DNA fragmentation. Mechanically, SeC caused mitochondrial dysfunction and imbalance of Bcl-2 family expression. SeC treatment also triggered ROS-mediated DNA damage and disturbed the MAPKs and AKT pathways. However, inhibition of ROS overproduction effectively attenuated SeC-induced oxidative damage and apoptosis, and normalized the expression of MAPKs and AKT pathways, indicating the significance of ROS in SeC-induced apoptosis. Importantly, U251 human glioma xenograft growth in nude mice was significantly inhibited in vivo. Further investigation revealed that SeC-induced oxidative damage was achieved by TrxR1-targeted inhibition in vitro and in vivo.

The findings validated the potential of SeC to inhibit human glioma growth by oxidative damage-mediated apoptosis through triggering TrxR1-targeted inhibition 3).


In a case-control study of glioma, Peeri et al., examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathwaywith the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study.

None of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70).

The present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome 4).

References

1)

Philipov P, Tzatchev K. Selenium in the treatment of patients with brain gliomas. A pilot study. Zentralbl Neurochir. 1990;51(3):145-6. PubMed PMID: 1965466.

2)

Yakubov E, Buchfelder M, Eyüpoglu IY, Savaskan NE. Selenium action in neuro-oncology. Biol Trace Elem Res. 2014 Dec;161(3):246-54. doi: 10.1007/s12011-014-0111-8. Epub 2014 Aug 28. Review. PubMed PMID: 25164034.

3)

Fan CD, Fu XY, Zhang ZY, Cao MZ, Sun JY, Yang MF, Fu XT, Zhao SJ, Shao LR, Zhang HF, Yang XY, Sun BL. Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk. Sci Rep. 2017 Jul 25;7(1):6465. doi: 10.1038/s41598-017-06979-2. PubMed PMID: 28743999; PubMed Central PMCID: PMC5526989.

4)

Peeri NC, Creed JH, Anic GM, Thompson RC, Olson JJ, LaRocca RV, Chowdhary SA, Brockman JD, Gerke TA, Nabors LB, Egan KM. Toenail selenium, genetic variation in selenoenzymes and risk and outcome in glioma. Cancer Epidemiol. 2018 May 16;55:45-51. doi: 10.1016/j.canep.2018.05.002. [Epub ahead of print] PubMed PMID: 29777993.

Update: Translaminar approach

Translaminar approach

In 1998, Di Lorenzo et al. proposed a less invasive direct procedure by utilizing a translaminar approach (TLA) through a fenestration of the pars interarticularis, thus circumventing facetectomy or hemilaminectomy in many cases. The increasing availability of high-definition imaging modalities (MRI, CT) has contributed to the growing popularity of the TLA, since identifying the exact location and extent of the spinal lesion is crucial for surgical planning to limit unnecessary biomechanical damage and prevent intraoperative conversion to conventional approaches.

Several studies have demonstrated the feasibility, safety and efficacy of this technique to successfully treat disc herniations affecting the foraminal and preforaminal regions 1).


The translaminar approach is the only “tissue-sparing” technique viable in cases of cranially migrated lumbar disc herniation encroaching on the exiting nerve root in the preforaminal zones, for the levels above L2-L3, and in the preforaminal and foraminal zones, for the levels below L3-L4 (L5-S1 included, if a total microdiscectomy is unnecessary). This approach is more effective than the standard one, because it resolves the symptoms; it is associated with less postoperative pain and faster recovery times without the risk of iatrogenic instability, and it can also be used in cases with previous signs of radiographic instability. The possibility to spare the flavum ligament is one of the main advantages of this technique. For these reasons, the translaminar approach is a valid technique in terms of safety and efficacy. Vanni et al., extensively analyzed and highlighted the tips and tricks 2).

Case series

2018

A consecutive series of 32 patients were divided, pre- and post-operatively, into 5 classes based on Oswestry Disability Index (ODI). Class 1: ODI 0-20% (minimal disability); class 2: 20-40 % (moderate disability); calss 3: 40-60% (severe disability); 60-80% (crippled); 80-100% (bed bound or exaggerating symptoms).

In terms of ODI, 4 (12.5%) patients upgraded of 1 class after the operation; 6 (18.7%) patients of 2 classes, 8 (25%) patients of 3 classes, 11 (34.4%) patients of 4 classes. Three (9.4%) patients did not modify their ODI score after the operation. After surgery, 7(21.9%) patients developed a mild low back pain. Mean follow-up was 25 months.

When performed by dedicated spinal neurosurgeons, the translaminar approach confirmed to be safe and effective in long-term follow-up. Moreover, the majority of patients showed an improvement of their ODI. Major pitfalls were related with surgical selection and the narrow working space 3).

2008

Between May 2000 and July 2004, 104 patients (59 men)-presenting with upper lumbar root compression in 74% of the cases -underwent a translaminar approach. The mean age was 57 years (range, 27-80 yr). The lamina was approached either through the conventional subperiosteal route or via a muscle splitting access. Mostly intraforaminal disc fragments were removed through a translaminar hole 10 mm in diameter, and the disc space was cleared in cases of evident perforation of the annulus. Follow-up examinations were performed by an independent observer at 1 and 6 weeks; 3, 6, and 12 months; and once yearly thereafter (mean follow-up period, 32 mo).

Extruded (61%) or subligamentous (39%) disc fragments were found intra-operatively. Laminae L4 (44%) and L5 (26%) were mostly involved. In eight cases, the translaminar hole was enlarged to a conventional laminotomy. In 13 patients, the disc space was cleared. The outcomes according to the Macnab criteria were excellent (67%), good (27%), fair (5%), and poor (1%). The incidence of recurrent disc herniations was 7%. Functional radiography performed in the first 20 patients 6 months after surgery and an additional 12 patients complaining of postsurgical back pain excluded any instability.

The translaminar approach is recommended in disc herniations encroaching the exiting root, as an alternative to the conventional interlaminar route4).

2007

Fifteen patients with far cranio-laterally extruded disc herniations underwent neurosurgical intervention using a translaminar approach. The paraspinal muscles were spread with a dilatator after performing a 1.5 cm skin incision. A 16 mm METRx tubular retractor system (Medtronic Sofamor Danek, Memphis, TN) was directly placed on the upper lamina. The next steps were performed through this channel using the surgical microscope. A small ovoid fenestration (10×5 mm) was performed using a high speed drill and the disc prolapse was removed in a standard manner. Follow-ups were routinely carried out 3 weeks postoperatively and reassessment was subsequently carried out by telephone inquiry 10 to 44 months (median 23 months) after treatment. These results were rated according to the modified MacNab criteria.

Five of the fifteen affected discs were at the level L3/4, eight at L4/5 and two at L5/S1. The average surgical time was 55 minutes. No complications occurred. In all patients sciatic pain disappeared immediately after the operation. One patient underwent fusion of the affected level one year later because of progression of a pre-existent pseudospondylolisthesis. Long-term follow-up demonstrated excellent results in six, good results in seven, a fair result in one and a poor result in one patient according to the modified MacNab criteria.

The translaminar approach in conjunction with a tubular retractor system seems to be an effective and safe alternative technique for treating the small entity of far cranio- laterally or foraminally extruded lumbar disc herniations. It combines the advantages of a blunt muscle-spreading approach that produces little damage to the soft tissues, and the avoidance of large bone removal that may jeopardize vertebral stability. Since this approach does not permit sufficient exploration of the intervertebral disc space of origin, it should be limited to patients without significant bulging of the disc itself 5).


Twenty-four patients with preforaminal and foraminal disc herniation underwent surgical treatment via a translaminar microsurgical approach. Excellent results were obtained in all patients in terms of pain relief, and all had improvement in motor strength except for 1 patient. No spinal instability was seen at the latest follow-up.

A classic interlaminar interspace approach combined with a very limited translaminar fenestration seem to be an acceptable surgical method for accessing a preforaminal disc herniation, and this technique has proven to be safe and did not cause any instability at the latest follow-up 6).

2002

30 patients using the translaminar fenestration were analysed by a postoperative follow-up of 6 weeks and one year. The mean-age was 57.2 years. For resection of the disc herniation, a small round or oval fenestration (6-8 mm) in the hemilamina, craniomedially to the facet joint, was performed. No patient received a partial or total facetectomy.

RESULTS: The majority of affected discs were at the L4-L5 level (53%). An extruded fragment was found in 28 patients (93%). In 5 patients bleeding from epidural veins complicated the intra-operative course. In 50% the nerve root was visually exposed. 15 patients (50%) had an intervertebral discectomy additional to the fragment excision. One patient was re-operated on after 10 days because of persisting radicular pain by using the same translaminar approach. 28 patients showed complete or nearly complete relief of radicular pain. Using this approach we have seen no major complication or clinical instability during a follow-up of at least one year.

CONCLUSIONS: The translaminar approach is an effective and minimally invasive technique in both canalicular and cranio-dorsolateral disc herniations. It gives an additional possibility to avoid partial removal of the facet joints, can be performed in all lumbar segments and preserves structures important for segmental spinal stability. The approach allows access to the extruded disc fragment and intervertebral disc space comparable to classical approaches and is a frequently used operative technique in our department 7).

1)

Di Lorenzo N, Porta F, Onnis G, Cannas A, Arbau G, Maleci A. Pars interarticularis fenestration in the treatment of foraminal lumbar disc herniation: a further surgical approach. Neurosurgery. 1998 Jan;42(1):87-9; discussion 89-90. PubMed PMID: 9442508.

2)

Vanni D, Galzio R, Kazakova A, Guelfi M, Pantalone A, Salini V, Magliani V. Technical note: microdiscectomy and translaminar approach. J Spine Surg. 2015 Dec;1(1):44-9. doi: 10.3978/j.issn.2414-469X.2015.10.03. Review. PubMed PMID: 27683678; PubMed Central PMCID: PMC5039873.

3)

Cossandi C, Fanti A, Gerosa A, Bianco A, Fornaro R, Crobeddu E, Forgnone S, Panzarasa G, Di Cristofori A. Translaminar approach for treatment of hidden zone foraminal lumbar disc herniations: considerations on the surgical technique and pre-operative selection of patients with a long term follow-up. World Neurosurg. 2018 May 18. pii: S1878-8750(18)31025-8. doi: 10.1016/j.wneu.2018.05.072. [Epub ahead of print] PubMed PMID: 29783010.

4)

Papavero L, Langer N, Fritzsche E, Emami P, Westphal M, Kothe R. The translaminar approach to lumbar disc herniations impinging the exiting root. Neurosurgery. 2008 Mar;62(3 Suppl 1):173-7; discussion 177-8. doi: 10.1227/01.neu.0000317389.83808.16. PubMed PMID: 18424983.

5)

Vogelsang JP. The translaminar approach in combination with a tubular retractor system for the treatment of far cranio-laterally and foraminally extruded lumbar disc herniations. Zentralbl Neurochir. 2007 Feb;68(1):24-8. PubMed PMID: 17487805.

6)

Bernucci C, Giovanelli M. Translaminar microsurgical approach for lumbar herniated nucleus pulposus (HNP) in the “hidden zone”: clinical and radiologic results in a series of 24 patients. Spine (Phila Pa 1976). 2007 Jan 15;32(2):281-4. PubMed PMID: 17224827.

7)

Soldner F, Hoelper BM, Wallenfang T, Behr R. The translaminar approach to canalicular and cranio-dorsolateral lumbar disc herniations. Acta Neurochir (Wien). 2002 Apr;144(4):315-20. PubMed PMID: 12021876.