Endoscopic surgery for intracerebral hemorrhage

Endoscopic surgery for intracerebral hemorrhage

Li et al. performed a study to explore the efficacy and safety of different surgical interventions in patients with spontaneous supratentorial intracranial hemorrhage (SSICH) and determine which intervention is most suitable for such patients.

They searched the PubMed, Medline, OVID, Embase, and Cochrane Library databases. The quality of the included studies was assessed. Statistical analyses were performed using the software Stata 13.0 and RevMan 5.3.

Endoscopic surgery (ES), minimally invasive surgery combined with urokinase (MIS + UK), minimally invasive surgery combined with recombinant tissue plasminogen activator (MIS + rt-PA), and craniotomy were associated with higher survival rates and a lower risk of intracranial rebleeding than standard medical care (SMC) in patients with SSICH, especially in younger patients with few comorbidities. The order from highest to lowest survival rate was ES, MIS + UK, MIS + rt-PA, craniotomy, and SMC. The order from lowest to highest intracranial rebleeding risk was ES, MIS + UK, craniotomy, MIS + rt-PA, and SMC. Additionally, compared with SMC, all four surgical interventions (ES, MIS + rt-PA, MIS + UK, and craniotomy) improved the prognosis and reduced the proportion of patients with serious disability. The order from most to least favorable prognosis was MIS + rt-PA, ES, MIS + UK, craniotomy, and SMC. The order from highest to lowest proportion of patients with serious disability was ES, MIS + rt-PA, MIS + UK, craniotomy, and SMC.

This study revealed that the efficacy and safety of different surgical interventions (ES, MIS + UK, MIS + rt-PA, craniotomy) were superior to those of SMC in the patients with SSICH, especially in younger patients with few comorbidities. Among them, ES was the most reasonable and effective intervention. ES was found not only to improve the survival rate and prognosis but also to have the lowest risk of intracranial rebleeding and the lowest proportion of patients with serious disability 1).


Some studies indicated that the endoscope-assisted keyhole approach might be an efficiency, safety, and minimal invasiveness surgical intervention for intracerebral hemorrhage 2) 3)

Controlled clinical trials are needed to evaluate the full potential and limitations of this promising technique 4).

The residual hematoma cannot be measured intraoperatively from the endoscopic view, and it is difficult to determine the precise location of the endoscope within the hematoma cavity.

Use of ultrasound guidance minimized the occurrence of brain injury due to hematoma evacuation 5).

Case series

Among 35 patients with putaminal or subcortical hemorrhage that was evacuated endoscopically, 14 cases (40%) presented both findings of neurological grade IV for severity and hematoma volume exceeding 70 mL in the recent 3 years (endoscope group), whereas 8 cases with the same conditions were treated by conventional craniotomy for the preceding 3-year period (craniotomy group). Between these two groups, mean age was higher and duration of surgery was shorter in the endoscope group, but no significant differences in hematoma size or evacuation rate were recognized. In the 10 cases that presented with signs of cerebral herniation (neurological grade IVb) and required emergent decompression, the preparation time for surgery tended to be shorter in the endoscope group, although the difference was not significant. Additional ventricular drainage was performed in 7 cases and showed a supplemental effect of reducing intracranial pressure (ICP). Consequently, all patients in the endoscope group were rescued without decompressive large craniectomy, even with symptoms of cerebral herniation. In conclusion, endoscopic surgery has the potential to offer an effective therapeutic option for comatose patients with large supratentorial intracerebral hemorrhages, matching conventional craniotomy for emergent treatment in terms of mortality and management of ICP 6).

Case reports

A 47-year-old man was admitted sustaining 13 points in Glasgow coma scale with brain computed tomography (CT) scan showing a temporal contusion. Guided by a 3D reconstructed CT, using the program OsiriX®, the posterior limit of the hematoma was identified. A burr hole was placed at the posterior temporal region, and we used the neuroendoscope to assist the hematoma evacuation. The postoperative tomography showed adequate hematoma removal. He was discharged from hospital 48 h after surgery. Two weeks later, he was conscious and oriented temporally. This endoscopic-assisted technique can provide safe removal of traumatic hematomas of the temporal lobe 7).

References

1)

Li M, Mu F, Su D, Han Q, Guo Z, Chen T. Different surgical interventions for patients with spontaneous supratentorial intracranial hemorrhage: A network meta-analysis. Clin Neurol Neurosurg. 2019 Nov 20;188:105617. doi: 10.1016/j.clineuro.2019.105617. [Epub ahead of print] PubMed PMID: 31775069.
2)

Nagasaka T, Tsugeno M, Ikeda H, Okamoto T, Inao S, Wakabayashi T. Early recovery and better evacuation rate in neuroendoscopic surgery for spontaneous intracerebral hemorrhage using a multifunctional cannula: preliminary study in comparison with craniotomy. Journal of Stroke & Cerebrovascular Diseases. 2011;20(3):208–213.
3)

Cho D-Y, Chen C-C, Chang C-S, Lee W-Y, Tso M. Endoscopic surgery for spontaneous basal ganglia hemorrhage: comparing endoscopic surgery, stereotactic aspiration, and craniotomy in noncomatose patients. Surgical Neurology. 2006;65(6):547–555.
4)

Beynon C, Schiebel P, Bösel J, Unterberg AW, Orakcioglu B. Minimally invasive endoscopic surgery for treatment of spontaneous intracerebral haematomas. Neurosurg Rev. 2015 Jul;38(3):421-8; discussion 428. doi: 10.1007/s10143-015-0606-6. Epub 2015 Feb 17. PubMed PMID: 25687253.
5)

Sadahiro H, Nomura S, Goto H, Sugimoto K, Inamura A, Fujiyama Y, Yamane A, Oku T, Shinoyama M, Suzuki M. Real-time ultrasound-guided endoscopic surgery for putaminal hemorrhage. J Neurosurg. 2015 Jun 5:1-5. [Epub ahead of print] PubMed PMID: 26047414.
6)

Yamashiro S, Hitoshi Y, Yoshida A, Kuratsu JI. Effectiveness of Endoscopic Surgery for Comatose Patients with Large Supratentorial Intracerebral Hemorrhages. Neurol Med Chir (Tokyo). 2015 Sep 11. [Epub ahead of print] PubMed PMID: 26369719.
7)

Nascimento CN, Amorim RL, Mandel M, do Espírito Santo MP, Paiva WS, Andrade AF, Teixeira MJ. Endoscopic-assisted removal of traumatic brain hemorrhage: case report and technical note. J Surg Case Rep. 2015 Nov 3;2015(11). pii: rjv132. doi: 10.1093/jscr/rjv132. PubMed PMID: 26537390.

Prophylactic plasma transfusion

Prophylactic plasma transfusion

Review findings show uncertainty for the utility and safety of prophylactic FFP use. This is due to predominantly very low-quality evidence that is available for its use over a range of clinically important outcomes, together with lack of confidence in the wider applicability of study findings, given the paucity or absence of study data in settings such as major body cavity surgery, extensive soft tissue surgery, orthopaedic surgery, or neurosurgery. Therefore, from the limited RCT evidence, we can neither support nor oppose the use of prophylactic FFP in clinical practice 1).


Prophylactic transfusion of plasma in severe traumatic brain injury without intracranial hemorrhage has not been demonstrated to improve outcome. In all situations of product transfusion, patients should be closely observed for signs of volume overload and the development of transfusion-related acute lung injury. The benefit of product transfusion should always be weighed against the risk of a transfusion-related complication 2).


West et al. in 2011 reviewed the literature in an attempt to clarify best clinical practice with regard to this issue. Although the activated partial thromboplastin time and prothrombin time-INR are useful laboratory tests to measure specific clotting factors in the coagulation cascade, in the absence of active bleeding or a preexisting coagulopathy, their utility as predictors of overall bleeding risk is limited. Several studies have shown an imperfect correlation between mild elevations in the INR and subsequent bleeding tendency. Furthermore, FFP transfusion is not always sufficient to achieve normal INR values in patients who have mild elevations (< 2) to begin with. Finally, there are risks associated with FFP transfusion, including potential transfusion-associated [disease] exposures as well as the time delay imposed by laboratory testing and transfusion administration prior to initiation of procedures. The authors propose that the current concept of a “normal” INR value warrants redefinition to make it a more meaningful clinical tool. Based on their review of the literature, the authors suggest that in a hemodynamically stable patient population there is a range of mildly prolonged INR values for which FFP transfusion is not beneficial, and is potentially harmful. 3)

In 2006 a paper presented the recommendations of the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSaPS; French Safety Agency for Health Products). A panel of experts reviewed and graded the literature on platelet transfusions; recommendations were formulated. Threshold platelet counts (PC) for transfusions in the perioperative context have not been clearly defined and should be determined by the existence of hemorrhagic risk factors. In the case of commonly practiced invasive procedures, the recommendation is to transfuse in order to achieve PC > 50,000 x microL-1. In the absence of platelet dysfunction, regardless of the type of surgery, the standard hemorrhagic risk threshold for surgery is 50,000 x microL-1. It has not been proven that the risk threshold is different according to the type of surgery. For neurosurgery and ophthalmologic surgery involving the posterior segment of the eye, a PC of 100,000 x microL-11 is required. For axial regional anesthesia, a PC of 50,000 x microL-11 is sufficient for spinal anesthesia; a PC of 80,000 x microL-11 has been proposed for epidurals. During massive transfusion, prophylactic platelet infusion cannot be recommended beyond a loss of two blood volumes in less than 24 h (Professional Consensus). As for the therapeutic transfusion of plasma and/or platelets, as much as possible, platelet deficit should be documented with test results (PC and fibrinogen) before transfusing. In the event of bleeding, platelet transfusion may precede plasma infusion. However, although this recommendation has been the subject of several professional consensus agreements, it is not based on any randomized studies. Threshold PC for perioperative transfusions have not been clearly defined and most recommendations are the result of a professional consensus 4)5).

References

1)

Huber J, Stanworth SJ, Doree C, Fortin PM, Trivella M, Brunskill SJ, Hopewell S, Wilkinson KL, Estcourt LJ. Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non-cardiac surgery or invasive procedures. Cochrane Database Syst Rev. 2019 Nov 28;11:CD012745. doi: 10.1002/14651858.CD012745.pub2. Review. PubMed PMID: 31778223.
2)

Reddy GD, Gopinath S, Robertson CS. Transfusion in Traumatic Brain Injury. Curr Treat Options Neurol. 2015 Nov;17(11):46. doi: 10.1007/s11940-015-0379-9. PubMed PMID: 26407615.
3)

West KL, Adamson C, Hoffman M. Prophylactic correction of the international normalized ratio in neurosurgery: a brief review of a brief literature. J Neurosurg. 2011 Jan;114(1):9-18. doi: 10.3171/2010.7.JNS091857. Epub 2010 Sep 3. Review. PubMed PMID: 20815695.
4)

Samama CM, Djoudi R, Lecompte T, Nathan N, Schved JF; French Health Products Safety Agency (AFSSAPS) Expert Group. Perioperative platelet transfusion. Recommendations of the French Health Products Safety Agency (AFSSAPS) 2003. Minerva Anestesiol. 2006 Jun;72(6):447-52. PubMed PMID: 16682914.
5)

Samama CM, Djoudi R, Lecompte T, Nathan-Denizot N, Schved JF; Agence Française de Sécurité Sanitaire des Produits de Santé expert group. Perioperative platelet transfusion: recommendations of the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSaPS) 2003. Can J Anaesth. 2005 Jan;52(1):30-7. PubMed PMID: 15625253.

5-aminolevulinic-acid guided resection

5-aminolevulinic-acid guided resection

In addition to stereotactic localization as well as intraoperative brain mapping, techniques to enhance visual identification of tumor intraoperatively may be used and include 5-aminolevulinic-acid (5-ALA). 5-ALA is metabolized into fluorescent porphyrins, which accumulate in malignant glioma cells. These property permits use of ultraviolet illumination during surgery as an adjunct to map out the tumor. This has been proven with RCT where the use of 5-ALA leads to more complete resection (65% vs. 36%, p < 0.0001), which translates into a higher 6-month progression-free survival (41% vs. 21.1%, p = 0.0003) but no effect on OS 1).


Fluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed 2)

Indications

Doses

The highest visible and measurable fluorescence was yielded by 20 mg/kg. No fluorescence was elicited at 0.2 mg/kg. Increasing 5-ALA doses did not result in proportional increases in tissue fluorescence or PPIX accumulation in plasma, indicating that doses higher than 20 mg/kg will not elicit useful increases in fluorescence 3).


Application of 5mg/kg ALA was evaluated as equally reliable as the higher dose regarding the diagnostic performance when guidance was performed using a spectroscopic system. Moreover, no PpIX was detected in the skin of the patients 4).

Over time, several other tumour entities have been identified to metabolize 5-ALA and show a similar fluorescence pattern during surgical resection.

Further research is warranted to determine the role of 5-ALA accumulation in post-ischaemic and inflammatory brain tissue 5).

The positive predictive values (PPVs), of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the negative predictive values (NPVs), of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence 6).

Reviews

Senders et al., systematically review all clinically tested fluorescent agents for application in fluorescence guided surgery (FGS) for glioma and all preclinically tested agents with the potential for FGS for glioma.

They searched the PubMed and Embase databases for all potentially relevant studies through March 2016.

They assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.

The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5 aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.

5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives. 7).

Complications

Despite its benefits, 5-ALA has not reached widespread popularity in the United States, primarily because of lack of Food and Drug Administration (FDA) approval. Even if it were approved, 5-ALA does have specific limitations including low depth of penetration, autofluorescence of background parenchyma


Findings suggest that the administration of 5-ALA or the combined effect of 5-ALA, anaesthesia and tumour resection can cause a mild and reversible elevation in liver enzymes. It therefore appears safe to change the regime of monitoring. Routine blood samples are thus abolished, though caution remains necessary in patients with known liver impairment 8).

For near infrared imaging, additional investigators have explored fluorescein as well as novel near-infrared (NIR) agents 9) 10) 11)

Stummer et al. showed that 5–ALA guided resections carry a higher risk of post-operative neurological deterioration than conventional resections (26% vs 15%, respectively), even though the difference vanished within weeks 12).

Just as tumour tissue is often indiscernible from normal brain tissue, functionally critical tissues are indistinguishable from tissues with less clinically relevant functions.

Thus, knowing when to stop a resection due to proximity to areas of crucial neurological functions is of obvious and utmost importance. Detailed knowledge of the normal brain anatomy and distribution of function is not sufficient during glioma resection. Interindividual variability and functional relocation (i.e., plasticity) induced by the presence of an infiltrating tumour 13) requires an exact functional brain map at the site of surgery in order to spare areas involved in crucial (so-called eloquent) functions. Preoperative localisation of function, either with functional MRI (fMRI) or navigated transcranial magnetic stimulation (nTMS), provides an approximate map 14) 15).

Furthermore, intra-operative direct cortical and subcortical electrical stimulation (DCS) for functional analysis of the tissue in the tumour’s infiltration zone is required for accurate identification of areas that need to be spared in order to retain the patient’s functional integrity 16) 17). Motor evoked potentials (MEP) provide real-time information on the integrity of the primary motor cortex and the corticospinal tract 18). Direct cortical mapping and phase reversal identify the primary motor and sensory cortices. Subcortical mapping can estimate the distance to the pyramidal tract, acting as guidance close to functionally critical areas 19). When integrated into the existing surgical tools, continuous and dynamic mapping enables more extensive resection while simultaneously protecting motor function 20). Using these techniques and a detailed electrophysiological “Bern-concept”, a group achieved complete motor function protection in 96% of patients with high-risk motor eloquent tumours 21). Furthermore, localisation of cortical and subcortical regions relevant to language function is essential for speech preservation during resection of gliomas in proximity to presumed speech areas 22) and requires the patient to be awake during the brain mapping part of surgery. Similarly, intra-operative mapping of visual functions may contribute to increased resections while avoiding tissue essential for vision within the temporal and occipital lobes 23).

References

1)

Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. PubMed PMID: 16648043.
2)

Hansen RW, Pedersen CB, Halle B, Korshoej AR, Schulz MK, Kristensen BW, Poulsen FR. Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study. J Neurosurg. 2019 Oct 4:1-8. doi: 10.3171/2019.6.JNS191531. [Epub ahead of print] PubMed PMID: 31585425.
3)

Stummer W, Stepp H, Wiestler OD, Pichlmeier U. Randomized, Prospective Double-Blinded Study Comparing 3 Different Doses of 5-Aminolevulinic Acid for Fluorescence-Guided Resections of Malignant Gliomas. Neurosurgery. 2017 Apr 1. doi: 10.1093/neuros/nyx074. [Epub ahead of print] PubMed PMID: 28379547.
4)

Haj-Hosseini N, Richter J, Hallbeck M, Wårdell K. Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery. Photodiagnosis Photodyn Ther. 2015 Mar 25. pii: S1572-1000(15)00031-9. doi: 10.1016/j.pdpdt.2015.03.004. [Epub ahead of print] PubMed PMID: 25818546.
5)

Behling F, Hennersdorf F, Bornemann A, Tatagiba M, Skardelly M. 5-Aminolevulinic acid accumulation in a cerebral infarction mimicking high-grade glioma, a case report. World Neurosurg. 2016 May 10. pii: S1878-8750(16)30271-6. doi: 10.1016/j.wneu.2016.05.009. [Epub ahead of print] PubMed PMID: 27178236.
6)

Lau D, Hervey-Jumper SL, Chang S, Molinaro AM, McDermott MW, Phillips JJ, Berger MS. A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas. J Neurosurg. 2015 Nov 6:1-10. [Epub ahead of print] PubMed PMID: 26544781.
7)

Senders JT, Muskens IS, Schnoor R, Karhade AV, Cote DJ, Smith TR, Broekman ML. Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results. Acta Neurochir (Wien). 2017 Jan;159(1):151-167. doi: 10.1007/s00701-016-3028-5. Review. PubMed PMID: 27878374; PubMed Central PMCID: PMC5177668.
8)

Offersen CM, Skjoeth-Rasmussen J. Evaluation of the risk of liver damage from the use of 5-aminolevulinic acid for intra-operative identification and resection in patients with malignant gliomas. Acta Neurochir (Wien). 2016 Nov 10. [Epub ahead of print] PubMed PMID: 27832337.
9)

Shinoda J, Yano H, Yoshimura SI, et al. Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note. J Neurosurg. 2003;99(3):597–603.
10)

Rey-Dios R, Cohen-Gadol AA. Technical principles and neurosurgical applications of fluorescein fluorescence using a microscope-integrated fluorescence module. Acta Neurochir (Wien). 2013;155(4):701–706.
11)

Swanson KI, Clark PA, Zhang RR, et al. Fluorescent cancer-selective alkylphosphocholine analogs for intraoperative glioma detection. Neurosurgery. 2015;76(2):115–123.
12)

Stummer W1, Tonn JC, Mehdorn HM, Nestler U, Franz K, Goetz C, et al. ALA-Glioma Study Group. Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5–aminolevulinic acid glioma resection study. J Neurosurg. 2011;114(3):613–23. doi: 10.3171/2010.3
13)

Ojemann G, Ojemann J, Lettich E, Berger M. Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients. J Neurosurg. 1989;71(3):316–26.
14)

Seghier ML, Lazeyras F, Pegna AJ, Annoni JM, Zimine I, Mayer E, et al. Variability of fMRI activation during a phonological and semantic language task in healthy subjects. Hum Brain Mapp. 2004;23(3):140–55.
15)

Krieg SM, Shiban E, Buchmann N, Gempt J, Foerschler A, Meyer B, et al. Utility of presurgical navigated transcranial magnetic brain stimulation for the resection of tumors in eloquent motor areas. J Neurosurg. 2012;116(5):994–1001. doi: 10.3171/2011.12.JNS111524
16) , 22)

Duffau H, Capelle L, Sichez N, Denvil D, Lopes M, Sichez JP, et al. Intraoperative mapping of the subcortical language pathways using direct stimulations. An anatomo-functional study. Brain. 2002;125(1):199–214.
17)

Duffau H, Capelle L, Denvil D, Sichez N, Gatignol P, Taillandier L, et al. Usefulness of intraoperative electrical subcortical mapping during surgery for low-grade gliomas located within eloquent brain regions: functional results in a consecutive series of 103 patients. J Neurosurg. 2003;98(4):764–78.
18)

Seidel K, Beck J, Stieglitz L, Schucht P, Raabe A. The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors. J Neurosurg. 2013;118(2):287–96.
19)

Seidel K, Beck J, Stieglitz L, Schucht P, Raabe A. Low Threshold Monopolar Motor Mapping for Resection of Primary Motor Cortex Tumors. Neurosurgery. 2012;71(1):104–14.
20)

Raabe A, Beck J, Schucht P, Seidel K. Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method. J Neurosurg. 2014;120(5)1015–24. doi: 10.3171/2014.1.JNS13909.
21)

Schucht P, Seidel K. Beck J, Murek M, Jilch A, Wiest R, et al. Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome. Neurosurg Focus. 2014;27(6):E16.
23)

Gras-Combe G, Moritz-Gasser S, Herbet G, Duffau H. Intraoperative subcortical electrical mapping of optic radiations in awake surgery for glioma involving visual pathways. J Neurosurg. 2012;117(3):466–73.
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