treatment

Chronic subdural hematoma treatment

Chronic subdural hematoma treatment

Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials 1).

Surgical therapies involve the irrigation and removal of the blood products, sometimes with partial resection of these vascular membranes 2).

Investigational medical therapies have employed various strategies, which include reducing the rate of microhemorrhage from the membranes, changing the osmotic environment, or altering angiogenesis 3).

Endovascular therapies are aimed at de-vascularizing these membranes 4) 5) 6) 7).

Providing a high level of evidence to propose a standard of care for this frequent pathology is of utmost importance. However, two surveys in the UK and in France have shown a wide range of practice, without major rationale 8) 9).

A variety of clinical factors must be taken into account in the treatment of chronic subdural hematoma (cSDH), and the multifaceted treatment paradigms continue to evolve 10).

There is lack of uniformity about the treatment strategies, such as the role of burr hole, twist drill, craniotomy, etc., in CSDH amongst various surgeons. There is also disagreement about the use of drain, irrigation, and steroid 11) 12).

Surgery is usually the treatment of choice, but conservative treatment may be a good alternative in some situations.

Chronic subdural hematoma surgery

see Chronic subdural hematoma surgery.

Middle Meningeal Artery Embolization

see Middle meningeal artery embolization for chronic subdural hematoma.

Systematic reviews

Chronic subdural hematoma recurrence after evacuation occurs in approximately 10% of chronic subdural hematomas, and the various Chronic subdural hematoma surgery interventions are approximately equivalent. Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials 13).

Soleman et al., provide a systematic review of studies analysing the conservative treatment options and the natural history of cSDH. Of 231 articles screened, 35 were included in this systematic review. Studies evaluating the natural history and conservative treatment modalities of cSDH remain sparse and are predominantly of low level of evidence. The natural history of cSDH remains unclear and is analysed only in case reports or very small case series. “Wait and watch” or “wait and scan” management is indicated in patients with no or minor symptoms (Markwalder score 0-1). However, it seems that there are no clear clinical or radiological signs indicating whether the cSDH will resolve spontaneously or not (type C recommendation). In symptomatic patients who are not worsening or in a comatose state, oral steroid treatment might be an alternative to surgery (type C recommendation). Tranexamic acid proved effective in a small patient series (type C recommendation), but its risk of increasing thromboembolic events in patients treated with antithrombotic or anticoagulant medication is unclear. Angiotensin converting-enzyme inhibitors were evaluated only as adjuvant therapy to surgery, and their effect on the rate of recurrence remains debatable. Mannitol showed promising results in small retrospective series and might be a valid treatment modality (type C recommendation). However, the long treatment duration is a major drawback. Patients presenting without paresis can be treated with a platelet activating factor receptor antagonist (type C recommendation), since they seem to promote resolution of the haematoma, especially in patients with subdural hygromas or low-density haematomas on computed tomography. Lastly, atorvastatin seems to be a safe option for the conservative treatment of asymptomatic or mildly symptomatic cSDH patients (type C recommendation). In conclusion, the knowledge of the conservative treatment modalities for cSDH is sparse and based on small case series and low grade evidence. However, some treatment modalities seem promising even in symptomatic patients with large haematomas. Randomised controlled trials are currently underway, and will hopefully provide us with good evidence for or against the conservative treatment of cSDH 14).

Surveys

The aim of a study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest 15).

Cenic et al. developed and administered a questionnaire to Canadian Neurosurgeons with questions relating to the management of chronic and subacute subdural hematoma. Our sampling frame included all neurosurgery members of the Canadian Neurosurgical Society.

Of 158 questionnaires, 120 were returned (response rate = 76%). The respondents were neurosurgeons with primarily adult clinical practices (108/120). Surgeons preferred one and two burr-hole craniostomy to craniotomy or twist-drill craniostomy as the procedure of choice for initial treatment of subdural hematoma (35.5% vs 49.5% vs 4.7% vs 9.3%, respectively). Craniotomy and two burr-holes were preferred for recurrent subdural hematomas (43.3% and 35.1%, respectively). Surgeons preferred irrigation of the subdural cavity (79.6%), use of a subdural drain (80.6%), and no use of anti-convulsants or corticosteroids (82.1% and 86.6%, respectively). We identified a lack of consensus with keeping patients supine following surgery and post-operative antibiotic use.

The survey has identified variations in practice patterns among Canadian Neurosurgeons with respect to treatment of subacute or chronic subdural hematoma (SDH). Our findings support the need for further prospective studies and clinical trials to resolve areas of discrepancies in clinical management and hence, standardize treatment regimens 16).

Steroids

Steroids for chronic subdural hematoma.

Goreisan

see Goreisan for chronic subdural hematoma

Chronic subdural hematoma seizure prophylaxis

see Chronic subdural hematoma seizure prophylaxis.

Anticoagulation resumption after chronic subdural hematoma

Anticoagulation resumption after chronic subdural hematoma.

References

1) , 13)

Henry J, Amoo M, Kissner M, Deane T, Zilani G, Crockett MT, Javadpour M. Management of Chronic Subdural Hematoma: A Systematic Review and Component Network Meta-analysis of 455 Studies With 103 645 Cases. Neurosurgery. 2022 Dec 1;91(6):842-855. doi: 10.1227/neu.0000000000002144. Epub 2022 Sep 28. PMID: 36170165.
2)

Markwalder TM . The course of chronic subdural hematomas after burr-hole craniostomy with and without closed-system drainage. Neurosurg Clin N Am 2000;11:541–6.doi:10.1016/S1042-3680(18)30120-7
3)

Sun TF , Boet R , Poon WS . Non-surgical primary treatment of chronic subdural haematoma: preliminary results of using dexamethasone. Br J Neurosurg 2005;19:327–33.doi:10.1080/02688690500305332
4)

Link TW , Boddu S , Marcus J , et al . Middle meningeal artery embolization as treatment for chronic subdural hematoma: a case series. Oper Neurosurg 2018;14:556–62.doi:10.1093/ons/opx154
5)

Link TW , Boddu S , Paine SM , et al . Middle meningeal artery embolization for chronic subdural hematoma: a series of 60 cases. Neurosurgery 2018;121.doi:10.1093/neuros/nyy521
6)

Link TW , Rapoport BI , Paine SM , et al . Middle meningeal artery embolization for chronic subdural hematoma: Endovascular technique and radiographic findings. Interv Neuroradiol 2018;24:455–62.doi:10.1177/1591019918769336
7)

Link TW , Schwarz JT , Paine SM , et al . Middle meningeal artery embolization for Chronic subdural hematoma recurrence: a case series. World Neurosurg 2018;118:e570–4.doi:10.1016/j.wneu.2018.06.241
8)

M. Guénot, Hématome sous-dural chronique. Introduction et résultats de l’enquête de la SFNC, Neurochirurgie 4 (2001) 459–460 https://doi.org/ NCHIR-11-2001-47- 5-0028-3770-101019-ART7.
9)

] T. Santarius, R. Lawton, P.J. Kirkpatrick, P.J. Hutchinson, The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland, Br. J. Neurosurg. 22 (2008) 529–534, https://doi.org/10.1080/02688690802195381.
10)

Sahyouni R, Goshtasbi K, Mahmoodi A, Tran DK, Chen JW. Chronic Subdural Hematoma: A Historical and Clinical Perspective. World Neurosurg. 2017 Dec;108:948-953. doi: 10.1016/j.wneu.2017.09.064. Epub 2017 Sep 19. Review. PubMed PMID: 28935548.
11) , 15)

Santarius T, Lawton R, Kirkpatrick PJ, Hutchinson PJ. The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland. Br J Neurosurg. 2008 Aug;22(4):529-34. doi: 10.1080/02688690802195381. PubMed PMID: 18686063.
12)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. PubMed PMID: 16408582.
14)

Soleman J, Noccera F, Mariani L. The conservative and pharmacological management of chronic subdural haematoma. Swiss Med Wkly. 2017 Jan 19;147:w14398. doi: smw.2017.14398. PubMed PMID: 28102879.
16)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. PubMed PMID: 16408582.

t

A variety of clinical factors must be taken into account in the treatment of chronic subdural hematoma (cSDH), and the multifaceted treatment paradigms continue to evolve 1).

There is lack of uniformity about the treatment strategies, such as the role of burr hole, twist drill, craniotomy, etc., in CSDH amongst various surgeons. There is also disagreement about the use of drain, irrigation, and steroid 2) 3).

Surgery is usually the treatment of choice, but conservative treatment may be a good alternative in some situations.

see DECSA trial.

see Middle Meningeal Artery Embolization.

Chronic subdural hematoma surgery

see Chronic subdural hematoma surgery.

Systematic reviews

Soleman et al., provide a systematic review of studies analysing the conservative treatment options and the natural history of cSDH. Of 231 articles screened, 35 were included in this systematic review. Studies evaluating the natural history and conservative treatment modalities of cSDH remain sparse and are predominantly of low level of evidence. The natural history of cSDH remains unclear and is analysed only in case reports or very small case series. “Wait and watch” or “wait and scan” management is indicated in patients with no or minor symptoms (Markwalder score 0-1). However, it seems that there are no clear clinical or radiological signs indicating whether the cSDH will resolve spontaneously or not (type C recommendation). In symptomatic patients who are not worsening or in a comatose state, oral steroid treatment might be an alternative to surgery (type C recommendation). Tranexamic acid proved effective in a small patient series (type C recommendation), but its risk of increasing thromboembolic events in patients treated with antithrombotic or anticoagulant medication is unclear. Angiotensin converting-enzyme inhibitors were evaluated only as adjuvant therapy to surgery, and their effect on the rate of recurrence remains debatable. Mannitol showed promising results in small retrospective series and might be a valid treatment modality (type C recommendation). However, the long treatment duration is a major drawback. Patients presenting without paresis can be treated with a platelet activating factor receptor antagonist (type C recommendation), since they seem to promote resolution of the haematoma, especially in patients with subdural hygromas or low-density haematomas on computed tomography. Lastly, atorvastatin seems to be a safe option for the conservative treatment of asymptomatic or mildly symptomatic cSDH patients (type C recommendation). In conclusion, the knowledge of the conservative treatment modalities for cSDH is sparse and based on small case series and low grade evidence. However, some treatment modalities seem promising even in symptomatic patients with large haematomas. Randomised controlled trials are currently underway, and will hopefully provide us with good evidence for or against the conservative treatment of cSDH 4).

Surveys

The aim of a study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest 5).

Cenic et al. developed and administered a questionnaire to Canadian Neurosurgeons with questions relating to the management of chronic and subacute subdural hematoma. Our sampling frame included all neurosurgery members of the Canadian Neurosurgical Society.

Of 158 questionnaires, 120 were returned (response rate = 76%). The respondents were neurosurgeons with primarily adult clinical practices (108/120). Surgeons preferred one and two burr-hole craniostomy to craniotomy or twist-drill craniostomy as the procedure of choice for initial treatment of subdural hematoma (35.5% vs 49.5% vs 4.7% vs 9.3%, respectively). Craniotomy and two burr-holes were preferred for recurrent subdural hematomas (43.3% and 35.1%, respectively). Surgeons preferred irrigation of the subdural cavity (79.6%), use of a subdural drain (80.6%), and no use of anti-convulsants or corticosteroids (82.1% and 86.6%, respectively). We identified a lack of consensus with keeping patients supine following surgery and post-operative antibiotic use.

The survey has identified variations in practice patterns among Canadian Neurosurgeons with respect to treatment of subacute or chronic subdural hematoma (SDH). Our findings support the need for further prospective studies and clinical trials to resolve areas of discrepancies in clinical management and hence, standardize treatment regimens 6).

Glucocorticoids

Since glucocorticoids have been used for treatment of cSDH in 1962 their role is still discussed controversially in lack of evident data. On the basis of the ascertained inflammation cycle in cSDH dexamethasone will be an ideal substance for a short lasting, concomitant treatment protocol.

A study is designed as a double-blind randomized placebo-controlled trial 820 patients who are operated for cSDH and from the age of 25 years are included after obtaining informed consent. They are randomized for administration of dexamethasone (16-16-12-12-8-4 mg/d) or placebo (maltodextrin) during the first 48 hours after surgery. The type I error is 5% and the type II error is 20%. The primary endpoint is the reoperation within 12 weeks postoperative.

This study tests whether dexamethasone administered over 6 days is a safe and potent agent in relapse prevention for evacuated cSDH 7).

Chronic subdural hematoma seizure prophylaxis

see Chronic subdural hematoma seizure prophylaxis.

Anticoagulation resumption after chronic subdural hematoma

Anticoagulation resumption after chronic subdural hematoma.

References

1)

Sahyouni R, Goshtasbi K, Mahmoodi A, Tran DK, Chen JW. Chronic Subdural Hematoma: A Historical and Clinical Perspective. World Neurosurg. 2017 Dec;108:948-953. doi: 10.1016/j.wneu.2017.09.064. Epub 2017 Sep 19. Review. PubMed PMID: 28935548.
2) , 5)

Santarius T, Lawton R, Kirkpatrick PJ, Hutchinson PJ. The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland. Br J Neurosurg. 2008 Aug;22(4):529-34. doi: 10.1080/02688690802195381. PubMed PMID: 18686063.
3)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. PubMed PMID: 16408582.
4)

Soleman J, Noccera F, Mariani L. The conservative and pharmacological management of chronic subdural haematoma. Swiss Med Wkly. 2017 Jan 19;147:w14398. doi: smw.2017.14398. PubMed PMID: 28102879.
6)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. PubMed PMID: 16408582.
7)

Emich S, Richling B, McCoy MR, Al-Schameri RA, Ling F, Sun L, Wang Y, Hitzl W. The efficacy of dexamethasone on reduction in the reoperation rate of chronic subdural hematoma – the DRESH study: straightforward study protocol for a randomized controlled trial. Trials. 2014 Jan 6;15(1):6. doi: 10.1186/1745-6215-15-6. PubMed PMID: 24393328; PubMed Central PMCID: PMC3891985.

Brain metastases treatment guidelines

Brain metastases treatment guidelines

ASCO-SNO-ASTRO Guideline 2022

https://ascopubs.org/doi/10.1200/JCO.21.02314?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours 2021

https://www.annalsofoncology.org/article/S0923-7534(21)02214-6/fulltext Published:August 05, 2021

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Surgery in the Management of Adults With Metastatic Brain Tumors 2019

Please see the full-text version of this guideline https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-treatment-of-adults-with-metastatic-bra-2 for the target population of each recommendation listed below.

SURGERY FOR METASTATIC BRAIN TUMORS AT NEW DIAGNOSIS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo Brain metastases surgery, Stereotactic radiosurgery for brain metastases (SRS), or whole brain radiotherapy (WBRT)?

RECOMMENDATIONS:

Level of Evidence 1: Surgery + WBRT is recommended as first-line treatment in patients with single brain metastases with favorable performance status and limited extracranial disease to extend overall survival, median survival, and local control.

Level of Evidence 3: Surgery plus SRS is recommended to provide survival benefit in patients with metastatic brain tumors

Level of Evidence 3: Multimodal treatments including either surgery + WBRT + SRS boost or surgery + WBRT are recommended as alternatives to WBRT + SRS in terms of providing overall survival and local control benefits.

SURGERY AND RADIATION FOR METASTATIC BRAIN TUMORS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo surgical resection followed by WBRT, SRS, or another combination of these modalities?

RECOMMENDATIONS:

Level 1: Surgery + WBRT is recommended as superior treatment to WBRT alone in patients with single brain metastases.

Level 3: Surgery + SRS is recommended as an alternative to treatment with SRS alone to benefit overall survival.

Level 3: It is recommended that SRS alone be considered equivalent to surgery + WBRT.

SURGERY FOR RECURRENT METASTATIC BRAIN TUMORS QUESTION: Should patients with recurrent metastatic brain tumors undergo surgical resection?

RECOMMENDATIONS:

Level 3: Craniotomy is recommended as a treatment for intracranial recurrence after initial surgery or SRS.   SURGICAL TECHNIQUE AND RECURRENCE QUESTION A: Does the surgical technique (en bloc resection or piecemeal resection) affect recurrence?

RECOMMENDATION:

Level 3: En bloc resection of the tumor, as opposed to piecemeal resection, is recommended to decrease the risk of postoperative leptomeningeal disease when resecting single brain metastases.

QUESTION B:

Does the extent of surgical resection (gross total resection or subtotal resection) affect recurrence?

RECOMMENDATION:

Level 3: Gross total resection is recommended over subtotal resection in Recursive partitioning analysis class 1 class I patients to improve overall survival and prolong time to recurrence. 1)

1)

Nahed BV, Alvarez-Breckenridge C, Brastianos PK, Shih H, Sloan A, Ammirati M, Kuo JS, Ryken TC, Kalkanis SN, Olson JJ. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Surgery in the Management of Adults With Metastatic Brain Tumors. Neurosurgery. 2019 Mar 1;84(3):E152-E155. doi: 10.1093/neuros/nyy542. PubMed PMID: 30629227.

Glioblastoma recurrence treatment

Glioblastoma recurrence treatment

There is no consensus as to the standard of care as no therapeutic options have produced substantial survival benefit for Glioblastoma recurrences (Glioblastomas) 1) 2).

A purely radiological diagnosis of recurrence or progression can be hampered by flaws induced by pseudoprogression, pseudoresponse, or radionecrosis

There is sufficient uncertainty and equipoise regarding the question of reoperation for patients with Glioblastoma recurrence to support the need for a randomized controlled trial 3).

Based on parameters like localization and tumor volume, patient’s Karnofsky Performance Score, time from initial diagnosis, and availability of alternative salvage therapies, reoperation can be considered as a treatment option to extend the overall survival and quality of life of the patient.

The achieved extent of resection of the relapsed tumor—especially with the intention of having a safe, complete resection of the enhancing tumor—most likely plays a crucial role in the ultimate outcome and prognosis of the patient, regardless of other modes of treatment. Validated scores to predict the prognosis after reoperation of a patient with a Glioblastoma recurrence can help to select suitable candidates for surgery. Safety issues and complication avoidance are pivotal to maximally preserving the patient’s quality of life. Besides a possible direct oncological effect, resampling of the recurrent tumor with detailed pathological and molecular analysis might have an impact on the development, testing, and validation of new salvage therapies 4).

Options

Options include repeat surgical resection, repeat fractionated radiation, radiosurgery.

Bevacizumab (BEV) plus daily temozolomide (TMZ) as a salvage therapy has been recommended for recurrent glioma.

In a study, Hundsberger et al investigated which treatments are currently being used for recurrent Glioblastoma within a single nation (Switzerland) and how clinicians are deciding to use them 5)

The authors surveyed Swiss hospitals with comprehensive multidisciplinary neuro-oncology practices (neurosurgery, radiation therapy, medical neuro-oncology, and a dedicated neuro-oncology tumor board) about treatment recommendations for recurrent Glioblastoma. They identified relevant clinical decision-making criteria, called diagnostic nodes or “dodes,” and compared treatment recommendations using a decision-tree format.

Eight hospitals participated. The most common treatment options for recurrent Glioblastoma were combination repeat surgical resection with temozolomide or bevacizumab, monotherapy temozolomide or bevacizumab, and best supportive care. Alternative therapies, including radiotherapy, were less common. Despite widespread disagreement between centers in clinical decision-making, the decision-tree analysis found agreement (>63%) between most centers for only 4 specific clinical scenarios. Patients without an appropriate performance status were usually managed with the best supportive care. Patients with rapid recurrence, nonresectable tumors, unmethylated O(6)-methylguanine DNA methyltransferase (MGMT) promoter, and high-performance status were usually managed with bevacizumab. Patients with late recurrence, nonresectable tumors, overt clinical symptoms, methylated MGMT promoter, multifocal disease, and high-performance status were usually managed with repeat temozolomide therapy. Patients with late recurrence, nonresectable tumors, no clinical symptoms, methylated MGMT promoter, tumor multifocality, and high-performance status were usually managed with temozolomide. The findings of this study underscore the lack of effective first- and second-line treatments for Glioblastoma, and the interhospital variability in practice patterns is not surprising. It seems likely that similar heterogeneity would also be noted in a study of American neuro-oncology centers. It is interesting to note that despite the availability of an increasing number of molecular markers for Glioblastoma stratification, MGMT promoter methylation appears to be the only biological marker widely used across multiple centers in this study. It remains to be seen when and how broadly other markers such as the epidermal growth factor receptor variant III or isocitrate dehydrogenase mutations will be adopted for clinical decision-making. The authors are to be congratulated for identifying core clinical decision-making criteria that may be useful in future studies of recurrent Glioblastoma. This decision tree is an excellent reference for clinical trial development, and several active clinical trials already target the dudes identified in this study. Subsequent studies may help to determine whether similar decision trees exist in American neuro-oncologic centers now or will exist in the future 6).

Figure. A through F, clinical decision-making tree for Glioblastoma recurrence multiforme (Glioblastoma) based on clinical scenarios that achieved a majority recommendation (ie, at least 5 of 8 Swiss hospitals). BEV, bevacizumab; BSC, best supportive care; rGlioblastoma, Glioblastoma recurrence multiforme; TMZ, temozolomide. Modified with kind permission from Springer Science+Business Media: Journal of Neuro-Oncology, Patterns of care in Glioblastoma recurrence in Switzerland: a multicenter national approach based on diagnostic nodes (published online ahead of print October 12. 2015), Hundsberger T, Hottinger AF, Roelcke U, et al [doi: 10.1007/s11060-015-1957-0. Available at: http://link.springer.com/article/10.1007%2Fs11060-015-1957-0 ].

Resection

see Glioblastoma recurrence resection.

Fractionated Stereotactic Radiotherapy

see Fractionated Stereotactic Radiotherapy for Glioblastoma recurrence.

Temozolomide

Temozolomide rechallenge is a treatment option for MGMT promoter-methylated Glioblastoma recurrence. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation 7).

Bevacizumab

see Bevacizumab for Glioblastoma recurrence.

Intraarterial chemotherapy

Intrarterial chemotherapy is a viable methodology in recurrent Glioblastoma patients to prolong survival at the risk of procedure-related complications and in newly diagnosed patients with the benefit of decreased complications 8).

Low-dose fractionated radiotherapy LD-FRT and chemotherapy for recurrent/progressive Glioblastoma have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted 9).

Second surgery plus carmustine wafers followed by intravenous fotemustine

Second surgery plus carmustine wafers followed by intravenous fotemustine in twenty-four patients were analyzed. The median age was 53.6; all patients had KPS between 90 and 100; 19 patients (79%) performed a gross total resection > 98% and 5 (21%) a gross total resection > 90%. The median progression-free survival from second surgery was 6 months (95% CI 3.9-8.05) and the median OS was 14 months (95% CI 11.1-16.8 months). Toxicity was predominantly haematological: 5 patients (21%) experienced grade 3-4 thrombocytopenia and 3 patients (12%) grade 3-4 leukopenia.

This multimodal strategy may be feasible in patients with Glioblastoma recurrence, in particular, for patients in good clinical conditions 10).

Immunotherapy

The HSPPC-96 vaccine is safe and warrants further study of efficacy for the treatment of recurrent Glioblastoma. Significant pretreatment lymphopenia may impact the outcomes of immunotherapy and deserves additional investigation 11).

Laser induced interstitial thermotherapy

see Laser interstitial thermotherapy.

Galldiks et al monitored the metabolic effects of stereotaxy-guided LITT in a patient with a recurrent Glioblastoma using amino acid positron emission tomography (PET). Serial 11C-methyl-L-methionine positron emission tomography (MET-PET) and contrast-enhanced computed tomography (CT) were performed using a hybrid PET/CT system in a patient with recurrent Glioblastoma before and after LITT. To monitor the biologic activity of the effects of stereotaxy-guided LITT, a threshold-based volume of interest analysis of the metabolically active tumor volume (MET uptake index of ≥ 1.3) was performed. A continuous decline in metabolically active tumor volume after LITT could be observed. MET-PET seems to be useful for monitoring the short-term therapeutic effects of LITT, especially when patients have been pretreated with a multistep therapeutic regimen. MET-PET seems to be an appropriate tool to monitor and guide experimental LITT regimens and should be studied in a larger patient group to confirm its clinical value 12).

CP-673451

CP-673451 for glioblastoma recurrence.

Lomustine

Adjuvant lomustine to other chemotherapy may provide no obvious benefits for the glioblastoma recurrence treatment 13).

Outcome

A more favorable prognosis following surgery for recurrence or progression is associated with younger age, smaller tumor volume (~50%), motor speech-middle cerebral artery scoring and preoperative Karnofsky performance score (KPS) >80% 14) 15).

Reviews

Optimal treatment for recurrent High-grade glioma continues to evolve. Currently, however, there is no consensus in the literature on the role of reoperation in the management of these patients.

An analysis, of reoperation in patients with World Health Organization grade III or IV recurrent gliomas, focusing on how reoperation affects outcome, perioperative complications, and quality of life. An extensive literature review was performed through the use of the PubMed and Ovid Medline databases for January 1980 through August 2013. A total 31 studies were included in the final analysis. Of the 31 studies with significant data from single or multiple institutions, 29 demonstrated a survival benefit or improved functional status after reoperation for recurrent high-grade glioma. Indications for reoperation included new focal neurological deficits, tumor mass effect, signs of elevated intracranial pressure, headaches, increased seizure frequency, and radiographic evidence of tumor progression. Age was not a contraindication to reoperation. Time interval of at least 6 months between operations and favorable performance status (Karnofsky Performance Status score ≥70) were important predictors of benefit from reoperation. Extent of resection at reoperation improved survival, even in patients with subtotal resection at initial operation. Careful patient selection such as avoiding those individuals with poor performance status and bevacizumab within 4 weeks of surgery is important. Although limited to retrospective analysis and patient selection bias, mounting evidence suggests a survival benefit in patients receiving a reoperation at the time of high-grade glioma recurrence 16).

Case series

2018

Twenty patients with recurrent glioma were treated with BEV (5-10 mg/kg, i.v. every 2 weeks) plus daily TMZ (daily, 50 mg/m2). The treatment response was evaluated via the RANO criteria. HRQL were measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (QLQ-C30) and Brain Module (QLQ-BN20).

Twenty patients received a total of 85 cycles of BEV with a median number of 4 cycles (range: 2-10). No patients showed complete response (CR) to treatment. Twelve patients had partial response (PR), stable disease (SD) in 5 patients with, and 3 patients showed progressive disease (PD). In the functioning domains of QLQ-C30, physical functioning, cognitive functioning and emotional functioning significantly improved after the second cycle of BEV compared to baseline, with the mean score of 45.0 vs. 64.0 (p = 0.020), 55.8 vs. 71.7 (p = 0.020) and 48.3 vs. 67.5 (p = 0.015), respectively. In the symptom scales, the scores of pain and nausea/vomiting significantly decreased compared to baseline from the mean score of 39.1 to 20.0 (p = 0.020) and 29.2 to 16.7 (p = 0.049), respectively. Score of global health status also increased from 47.5 to 63.3 (p = 0.001). As determined with the QLQ-BN20, motor dysfunction (43.3 vs. 25.0, p = 0.021), weakness of legs (36.7 vs. 18.3, p = 0.049), headache (38.3 vs. 20.0, p = 0.040), and drowsiness (50.0 vs. 30.0, p = 0.026) after the second cycle of BEV also significantly improved compared to baseline.

BEV plus daily TMZ as a salvage therapy improved HRQL in patients with recurrent glioma 17).

2016

Quick-Weller et al. performed tumour resections in seven patients with rGlioblastoma, combining 5-ALA (20 mg/kg bodyweight) with iMRI (0.15 T). Radiologically complete resections were intended in all seven patients.

They assessed intraoperative fluorescence findings and compared these with intraoperative imaging. All patients had early postoperative MRI (3 T) to verify final iMRI scans and received adjuvant treatment according to interdisciplinary tumour board decision.

Median patient age was 63 years. Median KPS score was 90, and median tumour volume was 8.2 cm(3). In six of seven patients (85%), 5-ALA induced fluorescence of tumour-tissue was detected intraoperatively. All tumours were good to visualise with iMRI and contrast media. One patient received additional resection of residual contrast enhancing tissue on intraoperative imaging, which did not show fluorescence. Radiologically complete resections according to early postoperative MRI were achieved in all patients. Median survival since second surgery was 7.6 months and overall survival since diagnosis was 27.8 months.

5-ALA and iMRI are important surgical tools to maximise tumour resection also in rGlioblastoma. However, not all rGlioblastomas exhibit fluorescence after 5-ALA administration. They propose the combined use of 5-ALA and iMRI in the surgery of rGlioblastoma 18).

Old publications

In some case series reoperation extends survival by an additional 36 weeks in patients with glioblastoma, and 88 weeks in anaplastic astrocytoma 19) 20) (duration of high-quality survival was 10 weeks and 83 weeks, respectively, and was lower with pre-op Karnofsky score < 70). In addition to Karnofsky performance score, significant prognosticators for response to repeat surgery include: age and time from the first operation to reoperation (shorter times → worse prognosis) 21). Morbidity is higher with reoperation (5–18%); the infection rate is ≈ 3x that for first operation, wound dehiscence is more likely

References

1)

Weller M, Cloughesy T, Perry JR, Wick W. Standards of care for treatment of Glioblastoma recurrence–are we there yet? Neuro Oncol. 2013 Jan;15(1):4-27. doi: 10.1093/neuonc/nos273. Epub 2012 Nov 7. Review. PubMed PMID: 23136223; PubMed Central PMCID: PMC3534423.
2)

Lukas RV, Mrugala MM (2017) Pivotal trials for infiltrating gliomas and how they affect clinical practice. Neuro Oncol Pract 4:209–219
3)

Patel M, Au K, Davis FG, Easaw JC, Mehta V, Broad R, Chow MMC, Hockley A, Kaderali Z, Magro E, Nataraj A, Scholtes F, Chagnon M, Gevry G, Raymond J, Darsaut TE. Clinical Uncertainty and Equipoise in the Management of Glioblastoma recurrence. Am J Clin Oncol. 2021 Mar 29. doi: 10.1097/COC.0000000000000812. Epub ahead of print. PMID: 33782334.
4)

Dejaegher J, De Vleeschouwer S. Recurring Glioblastoma: A Case for Reoperation? In: De Vleeschouwer S, editor. Glioblastoma [Internet]. Brisbane (AU): Codon Publications; 2017 Sep 27. Chapter 14. Available from http://www.ncbi.nlm.nih.gov/books/NBK469991/ PubMed PMID: 29251867.
5)

Hundsberger T, Hottinger AF, Roelcke U, et al.. Patterns of care in Glioblastoma recurrence in Switzerland: a multicentre national approach based on diagnostic nodes [published online ahead of print October 12, 2015]. J Neuro Oncol. doi: 10.1007/s11060-015-1957-0. Available at: http://link.springer.com/article/10.1007%2Fs11060-015-1957-0.
6)

Zussman BM, Engh JA. Patterns of Care and Clinical Decision Making for Glioblastoma recurrence Multiforme. Neurosurgery. 2016 Feb;78(2):N12-4. doi: 10.1227/01.neu.0000479889.72124.20. PubMed PMID: 26779791.
7)

Weller M, Tabatabai G, Kästner B, Felsberg J, Steinbach JP, Wick A, Schnell O, Hau P, Herrlinger U, Sabel MC, Wirsching HG, Ketter R, Bähr O, Platten M, Tonn JC, Schlegel U, Marosi C, Goldbrunner R, Stupp R, Homicsko K, Pichler J, Nikkhah G, Meixensberger J, Vajkoczy P, Kollias S, Hüsing J, Reifenberger G, Wick W; DIRECTOR Study Group. MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial. Clin Cancer Res. 2015 May 1;21(9):2057-64. doi: 10.1158/1078-0432.CCR-14-2737. Epub 2015 Feb 5. PubMed PMID: 25655102.
8)

Theodotou C, Shah AH, Hayes S, Bregy A, Johnson JN, Aziz-Sultan MA, Komotar RJ. The role of intra-arterial chemotherapy as an adjuvant treatment for glioblastoma. Br J Neurosurg. 2014 Jan 16. [Epub ahead of print] PubMed PMID: 24432794.
9)

Balducci M, Diletto B, Chiesa S, D’Agostino GR, Gambacorta MA, Ferro M, Colosimo C, Maira G, Anile C, Valentini V. Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma : Final report of a pilot study. Strahlenther Onkol. 2014 Jan 17. [Epub ahead of print] PubMed PMID: 24429479.
10)

Lombardi G, Della Puppa A, Zustovich F, Pambuku A, Farina P, Fiduccia P, Roma A, Zagonel V. The combination of carmustine wafers and fotemustine in recurrent glioblastoma patients: a monoinstitutional experience. Biomed Res Int. 2014;2014:678191. doi: 10.1155/2014/678191. Epub 2014 Apr 9. PubMed PMID: 24812626.
11)

Bloch O, Crane CA, Fuks Y, Kaur R, Aghi MK, Berger MS, Butowski NA, Chang SM, Clarke JL, McDermott MW, Prados MD, Sloan AE, Bruce JN, Parsa AT. Heat-shock protein peptide complex-96 vaccination for Glioblastoma recurrence: a phase II, single-arm trial. Neuro Oncol. 2013 Dec 12. [Epub ahead of print] PubMed PMID: 24335700.
12)

Galldiks N, von Tempelhoff W, Kahraman D, Kracht LW, Vollmar S, Fink GR, Schroeter M, Goldbrunner R, Schmidt M, Maarouf M. 11C-methionine positron emission tomographic imaging of biologic activity of a Glioblastoma recurrence treated with stereotaxy-guided laser-induced interstitial thermotherapy. Mol Imaging. 2012 Jul-Aug;11(4):265-71. PubMed PMID: 22954142.
13)

Fu X, Shi D, Feng Y. The Efficacy and Safety of Adjuvant Lomustine to Chemotherapy for Recurrent Glioblastoma: A Meta-analysis of Randomized Controlled Studies. Clin Neuropharmacol. 2022 Nov-Dec 01;45(6):162-167. doi: 10.1097/WNF.0000000000000525. PMID: 36383914.
14)

Barbagallo GM, Jenkinson MD, Brodbelt AR. ‘Recurrent’ glioblastoma multiforme, when should we reoperate? Br J Neurosurg. 2008 Jun;22(3):452-5. doi: 10.1080/02688690802182256. Review. PubMed PMID: 18568742.
15)

Park JK, Hodges T, Arko L, Shen M, Dello Iacono D, McNabb A, Olsen Bailey N, Kreisl TN, Iwamoto FM, Sul J, Auh S, Park GE, Fine HA, Black PM. Scale to predict survival after surgery for Glioblastoma recurrence multiforme. J Clin Oncol. 2010 Aug 20;28(24):3838-43. doi: 10.1200/JCO.2010.30.0582. Epub 2010 Jul 19. PubMed PMID: 20644085; PubMed Central PMCID: PMC2940401.
16)

Hervey-Jumper SL, Berger MS. Reoperation for recurrent high-grade glioma: a current perspective of the literature. Neurosurgery. 2014 Nov;75(5):491-9; discussion 498-9. doi: 10.1227/NEU.0000000000000486. PubMed PMID: 24991712.
17)

Liu Y, Feng F, Ji P, Liu B, Ge S, Yang C, Lou M, Liu J, Li B, Gao G, Qu Y, Wang L. Improvement of health related quality of life in patients with recurrent glioma treated with bevacizumab plus daily temozolomide as the salvage therapy. Clin Neurol Neurosurg. 2018 Mar 27;169:64-70. doi: 10.1016/j.clineuro.2018.03.026. [Epub ahead of print] PubMed PMID: 29631109.
18)

Quick-Weller J, Lescher S, Forster MT, Konczalla J, Seifert V, Senft C. Combination of 5-ALA and iMRI in re-resection of Glioblastoma recurrence. Br J Neurosurg. 2016 Jun;30(3):313-7. doi: 10.3109/02688697.2015.1119242. Epub 2016 Jan 8. PubMed PMID: 26743016.
19)

Harsh GR, Levin VA, Gutin PH, et al. Reoperation for Glioblastoma recurrence and Anaplastic Astrocytoma. Neurosurgery. 1987; 21:615–621
20)

Ammirati M, Galicich JH, Arbit E, et al. Reoperation in the Treatment of Recurrent Intracranial Malignant Gliomas. Neurosurgery. 1987; 21:607–614
21)

Brem H, Piantadosi S, Burger PC, et al. Placebo- Controlled Trial of Safety and Efficacy of Intraoperative Controlled Delivery by Biodegradable Polymers of Chemotherapy for Recurrent Gliomas. Lancet. 1995; 345:1008–1012

Vestibular schwannoma treatment

Vestibular schwannoma treatment

Optimal decision making in new diagnosed vestibular schwannoma remains a matter of debate. For small- to medium-sized lesions (Koos grading scale I–III), the options are radiosurgery (RS), microsurgery, or a “wait and-scan” approach 1).

This is mainly based on the hospital setting, as well as surgeon’s preference. It is worth noting that comparative studies advocate that GKS compares favorably with microsurgery, with high local tumor control, much lower rate of facial nerve palsy, and much higher rate of serviceable hearing preservation 2) 3) 4) 5) 6).

Conservative treatment

see Vestibular schwannoma conservative treatment.

Fractionated stereotactic radiotherapy

see Fractionated stereotactic radiotherapy for vestibular schwannoma

Radiosurgery

see Vestibular schwannoma radiosurgery.

Surgery

see Vestibular schwannoma surgery.

Subjects presented to the Department of Otolaryngology-Head and Neck Surgery and the Department of Neurosurgery at the Johns Hopkins University, Baltimore, Maryland for management of unilateral vestibular schwannoma from 1997 through 2007, with at least two visits within the first year of presentation. The proportion of patients for whom initial management consisted of observation, surgical resection, or radiation therapy was determined, and the relative influence of study year, patient age, hearing status, and tumor size was analyzed.

RESULTS: Over the study period there was an increase in the proportion of cases that were observed with follow-up scanning (10.5% to 28.0%) and recommended for radiation (0% to 4.0%), whereas the proportion of operated cases declined (89.5% to 68.0%). There were no changes in mean age or hearing status at diagnosis, but mean tumor size declined significantly. Compared to those undergoing surgery, patients choosing observation and radiation therapy were on average 11.7 and 4.5 years older, respectively. Tumors that were surgically removed were on average 11.6 mm larger than those that were observed. The increasing frequency over time of observation relative to surgery was significant even after controlling for age, hearing status, and tumor size.

CONCLUSIONS: Among patients managed by our center, there has been a significant shift in management of vestibular schwannomas over the last decade, with increasing tendency towards observation. This trend implies changing provider philosophy and patient expectations 7).

Patients with VS completed a voluntary survey over a 3-month period. Setting Surveys were distributed online through email, Facebook, and member website. Subjects and Methods All patients had a diagnosis of VS and were members of the Acoustic Neuroma Association (ANA). A total of 789 patients completed the online survey. Results Of the 789 participants, 474 (60%) cited physician recommendation as a significant influential factor in deciding treatment. In our sample, 629 (80%) saw multiple VS specialists and 410 (52%) sought second opinions within the same specialty. Of those who received multiple consults, 242 (59%) of patients reported receiving different opinions regarding treatment. Those undergoing observation spent significantly less time with the physician (41 minutes) compared to surgery (68 minutes) and radiation (60 minutes) patients ( P < .001). A total of 32 (4%) patients stated the physician alone made the decision for treatment, and 29 (4%) felt they did not understand all possible treatment options before final decision was made. Of the 414 patients who underwent surgery, 66 (16%) felt they were pressured by the surgeon to choose surgical treatment. Conclusion Deciding on a proper VS treatment for patients can be complicated and dependent on numerous clinical and individual factors. It is clear that many patients find it important to seek second opinions from other specialties. Moreover, second opinions within the same specialty are common, and the number of neurotologists consulted correlated with higher decision satisfaction 8).

From a total of 8330 patients (average age 54.7 years, 51.9% female) were analyzed and from 2004 to 2011, there was a statistically significant decrease in tumor size category at time of diagnosis (P < .01). Overall, 3982 patients (48%) received primary microsurgery, 1978 (24%) radiation therapy alone, and 2370 (29%) observation. Within the microsurgical cohort, 732 (18%) underwent subtotal resection, and of those, 98 (13.4%) received postoperative radiation therapy. Multivariable regression revealed that surgical treatment was more common in younger patients and larger tumor size categories (P < .05). Management trend analysis revealed that microsurgery was used less frequently over time (P < .0001), observation was used more frequently (P < .0001), and the pattern of radiation therapy remained unchanged. Linear regression was used to create an equation that was applied to predict future management practices. These data predict that by 2026, half of all cases of VS will be managed initially with observation.

While the incidence of VS has remained steady, tumor size at time of diagnosis has decreased over time. Within the United States there has been a clear, recent evolution in management toward observation 9).

Immunotherapy

Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. These findings provide a rationale for clinical trials evaluating immunotherapy in patients with rapidly progressing VS 10)

1)

Kondziolka D, Mousavi SH, Kano H, Flickinger JC, Lunsford LD. The newly diagnosed vestibular schwannoma: radiosurgery, resection, or observation? Neurosurg Focus 2012;33(03):E8
2)

Pollock BE, Lunsford LD, Kondziolka D, et al. Outcome analysis of acoustic neuroma management: a comparison of microsurgery and stereotactic radiosurgery. Neurosurgery 1995;36(01):215- –224, discussion 224–229
3)

Régis J, Pellet W, Delsanti C, et al. Functional outcome after Gamma knife radiosurgery or microsurgery for vestibular schwannomas. J Neurosurg 2002;97(05):1091–1100
4)

Myrseth E, Møller P, Pedersen PH, Vassbotn FS, Wentzel-Larsen T, Lund-Johansen M. Vestibular schwannomas: clinical results and quality of life after microsurgery or Gamma Knife radiosurgery. Neurosurgery 2005;56(05):927–935, discussion 927– 935
5)

Myrseth E, Møller P, Pedersen PH, Lund-Johansen M. Vestibular schwannoma: surgery or Gamma Knife radiosurgery? A prospective, nonrandomized study. Neurosurgery 2009;64(04):654–661, discussion 661–663
6)

Pollock BE, Driscoll CL, Foote RL, et al. Patient outcomes after vestibular schwannoma management: a prospective comparison of microsurgical resection and stereotactic radiosurgery. Neurosurgery 2006;59(01):77–85, discussion 77–85
7)

Tan M, Myrie OA, Lin FR, Niparko JK, Minor LB, Tamargo RJ, Francis HW. Trends in the management of vestibular schwannomas at Johns Hopkins 1997-2007. Laryngoscope. 2010 Jan;120(1):144-9. doi: 10.1002/lary.20672. PubMed PMID: 19877188.
8)

Moshtaghi O, Goshtasbi K, Sahyouni R, Lin HW, Djalilian HR. Patient Decision Making in Vestibular Schwannoma: A Survey of the Acoustic Neuroma Association. Otolaryngol Head Neck Surg. 2018 Feb 1:194599818756852. doi: 10.1177/0194599818756852. [Epub ahead of print] PubMed PMID: 29436268.
9)

Carlson ML, Habermann EB, Wagie AE, Driscoll CL, Van Gompel JJ, Jacob JT, Link MJ. The Changing Landscape of Vestibular Schwannoma Management in the United States-A Shift Toward Conservatism. Otolaryngol Head Neck Surg. 2015 Jun 30. pii: 0194599815590105. [Epub ahead of print] PubMed PMID: 26129740.
10)

Amit M, Xie T, Gleber-Netto FO, Hunt PJ, Mehta GU, Bell D, Silverman DA, Yaman I, Ye Y, Burks JK, Fuller GN, Gidley PW, Nader ME, Raza SM, DeMonte F. Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology. J Exp Clin Cancer Res. 2022 Oct 4;41(1):292. doi: 10.1186/s13046-022-02473-4. PMID: 36195959.

Parkinson’s Disease Treatment Guidelines

Parkinson’s Disease Treatment Guidelines

An update of the Parkinson’s Disease treatment Guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist should know the therapies and their place in the treatment pathway.

Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the spectrum of approved interventions including deep brain stimulation (DBS) or brain lesioning with different techniques (radiofrequency thermocoagulation, radiosurgery, magnetic resonance imaging-guided focused ultrasound surgery [MRgFUS] of the following targets: subthalamic nucleus [STN], ventrolateral thalamus, and pallidum internum [GPi]). Continuous delivery of medication subcutaneously (apomorphine pump) or through percutaneous ileostomy (Intrajejunal levodopa-carbidopa therapy) [LCIG]) was also included. Changes in motor features, health-related quality of life (QoL), adverse effects, and further outcome parameters were evaluated. Recommendations were based on high-class evidence and graded in three gradations. If only lower class evidence was available but the topic was felt to be of high importance, a clinical consensus of the guideline task force was gathered.

Two research questions have been answered with eight recommendations and five clinical consensus statements. Invasive therapies are reserved for specific patient groups and clinical situations mostly in the advanced stage of Parkinson’s disease (PD). Interventions may be considered only for special patient profiles, which are mentioned in the text. Therapy effects are reported as a change compared with current medical treatment. Subthalamic deep brain stimulation for Parkinson’s disease is the best-studied intervention for advanced disease with fluctuations not satisfactorily controlled with oral medications; it improves motor symptoms and QoL, and treatment should be offered to eligible patients. GPi-DBS can also be offered. For early PD with early fluctuations, STN-DBS is likely to improve motor symptoms, and QoL and can be offered. DBS should not be offered to people with early PD without fluctuations. LCIG and an apomorphine pump can be considered for advanced PD with fluctuations not sufficiently managed with oral treatments. Unilateral MRgFUS of the STN can be considered for distinctly unilateral PD within registries. The clinical consensus was reached on the following statements: Radiosurgery with gamma radiation cannot be recommended, unilateral radiofrequency thermocoagulation of the pallidum for advanced PD with treatment-resistant fluctuations, and unilateral radiofrequency thermocoagulation of the thalamus for resistant tremor can be recommended if other options are not available, unilateral MRgFUS of the thalamus for medication-resistant tremor of PD can be considered only within registries, and unilateral MRgFUS of the pallidum is not recommended.

Evidence for invasive therapies in PD is heterogeneous. Only some of these therapies have a strong scientific basis 1) 2).

European Academy of Neurology/Movement Disorder Society-European Section Guidelines on Pallidotomy for Parkinson’s Disease 3).

1)

Deuschl G, Antonini A, Costa J, Śmiłowska K, Berg D, Corvol JC, Fabbrini G, Ferreira J, Foltynie T, Mir P, Schrag A, Seppi K, Taba P, Ruzicka E, Selikhova M, Henschke N, Villanueva G, Moro E. European Academy of Neurology/Movement Disorder Society-European Section Guideline on the Treatment of Parkinson’s Disease: I. Invasive Therapies. Mov Disord. 2022 Jul;37(7):1360-1374. doi: 10.1002/mds.29066. Epub 2022 Jul 6. PMID: 35791767.
2)

Deuschl G, Antonini A, Costa J, Śmiłowska K, Berg D, Corvol JC, Fabbrini G, Ferreira J, Foltynie T, Mir P, Schrag A, Seppi K, Taba P, Ruzicka E, Selikhova M, Henschke N, Villanueva G, Moro E. European Academy of Neurology/Movement Disorder Society – European Section guideline on the treatment of Parkinson’s disease: I. Invasive therapies. Eur J Neurol. 2022 Sep;29(9):2580-2595. doi: 10.1111/ene.15386. Epub 2022 Jul 6. PMID: 35791766.
3)

Hariz M, Bronstein JM, Cosgrove GR, de Bie RMA, DeLong MR, Gross RE, Krack P, Krauss JK, Lang AE, Lees AJ, Lozano AM, Obeso JA, Schuurman PR, Vitek JL. European Academy of Neurology/Movement Disorder Society-European Section Guidelines on Pallidotomy for Parkinson’s Disease: Let’s Be Accurate. Mov Disord. 2022 Sep 1. doi: 10.1002/mds.29210. Epub ahead of print. PMID: 36047463.

Anterior communicating artery aneurysm endovascular treatment complications

Anterior communicating artery aneurysm endovascular treatment complications

Intraprocedural aneurysm rupture and thrombus formation are serious complications during coiling of ruptured intracranial aneurysms, and they more often occur in patients with anterior communicating artery aneurysms.

It is associated with a high rate of complete angiographic occlusion. However, the procedure-related permanent morbidity and mortality are not negligible for aneurysms in this location 1).

Delgado Acosta et al. from Hospital Universitario Reina Sofía aimed to report the characteristics of patients suffering intra- or peri-procedural ruptures during embolization of cerebral aneurysms.

Between March 1994 and October 2021, 648 consecutive cerebral aneurysms were treated by the endovascular procedure. Medical records were reviewed retrospectively with emphasis on procedure description, potential risk factors, and clinical outcomes related to intra- or peri-procedural rupture.

Of the 648 patients, 17 (2.6%) suffered an intra- or peri-procedural hemorrhagic event. The most common location was the anterior communicating artery. There was no significant difference between previously ruptured and unruptured aneurysms in the incidence of bleeding. In four patients, bleeding was evident within 24 h after the procedure. The clinical evolution at three months was poor and only four patients presented a positive evolution. There were 11 deaths (64.71%). Balloon remodeling was associated with an increased frequency of ruptures, while stenting was a safer treatment.

Aneurysm rupture during endovascular therapy is unpredictable, and its occurrence can be devastating. The incidence is quite low although the outcome is frequently poor. Early detection and proper management, including prompt occlusion of the aneurysm, are important to achieve a positive outcome. Anterior communicating artery aneurysms and those treated with balloon catheters have a higher incidence of rupture. A small number of ruptures of uncertain origin occur that go unnoticed in digital subtraction angiograms 2).

The immediate and long-term outcomes, complications, recurrences and the need for retreatment were analyzed in a series of 280 consecutive patients with anterior communicating artery aneurysms treated with the endovascular technique. From October 1992 to October 2001 280 patients with 282 anterior communicating artery aneurysms were addressed to our center. For the analysis, the population was divided into two major groups: group 1, comprising 239 (85%) patients with ruptured aneurysms and group 2 comprising of 42 (15%) patients with unruptured aneurysms. In group 1, 185 (77.4%) patients had a good initial pre-treatment Hunt and Hess grade of I-III. Aneurysm size was divided into three categories according to the larger diameter: less than 4 mm, between 4 and 10 mm and larger than 10 mm. The sizes of aneurysms in groups 1 and 2 were identical but a less favorable neck to depth ratio of 0.5 was more frequent in group 2. Endovascular treatment was finally performed in 234 patients in group 1 and 34 patients in group 2. Complete obliteration was more frequently obtained in group 2 unlike a residual neck or opacification of the sac that were more frequently seen in group 1. No peri-treatment complications were recorded in group 2. In group 1 the peri-treatment mortality and overall peri-treatment morbidity were 5.1% and 8.1% respectively. Eight patients (3.4%) in group 1 presented early post treatment rebleeding with a mortality of 88%. The mean time to follow-up was 3.09 years. In group 1, 51 (21.7%) recurrences occurred of which 14 were minor and 37 major. In group 2, eight (23.5%) recurrences occurred, five minor and three major. Two patients (0.8%) presented late rebleeding in group 1. Twenty-seven second endovascular retreatments were performed, 24 (10.2%) in group 1 and three (8.8%) in group 2, seven third endovascular retreatments and two surgical clippings in group 1 only. There was no additional morbidity related to retreatments. Endovascular treatment is an effective method for the treatment of anterior communicating artery aneurysms allowing late rebleeding prevention. Peri-treatment rebleeding warrants caution in anticoagulation management. This is a single center experience and the follow-up period is limited. Patients should be followed-up in the long-term as recurrences may occur and warrant additional treatment 3).

Prolonged anterograde amnesia and disorientation after anterior communicating artery aneurysm coil embolization 4)

LVIS stent-assisted coiling for ruptured wide-necked ACoA aneurysms was safe and effective, with a relatively low rate of perioperative complications and a high rate of complete occlusion at follow-up 5)

1)

Fang S, Brinjikji W, Murad MH, Kallmes DF, Cloft HJ, Lanzino G. Endovascular treatment of anterior communicating artery aneurysms: a systematic review and meta-analysis. AJNR Am J Neuroradiol. 2014 May;35(5):943-7. doi: 10.3174/ajnr.A3802. Epub 2013 Nov 28. PMID: 24287090; PMCID: PMC7964525.
2)

Delgado Acosta F, Bravo Rey I, Jiménez Gómez E, Saucedo VR, Toledano A, Oteros Fernández R. Intra- or peri-procedural rupture in the endovascular treatment of intracranial aneurysms. Acta Neurol Scand. 2022 Aug 17. doi: 10.1111/ane.13686. Epub ahead of print. PMID: 35975464.
3)

Finitsis S, Anxionnat R, Lebedinsky A, Albuquerque PC, Clayton MF, Picard L, Bracard S. Endovascular treatment of ACom intracranial aneurysms. Report on series of 280 patients. Interv Neuroradiol. 2010 Mar;16(1):7-16. doi: 10.1177/159101991001600101. Epub 2010 Mar 25. PMID: 20377974; PMCID: PMC3277962.
4)

Al-Atrache Z, Friedler B, Shaikh HA, Kavi T. Prolonged anterograde amnesia and disorientation after anterior communicating artery aneurysm coil embolisation. BMJ Case Rep. 2019 Jul 30;12(7). pii: e230543. doi: 10.1136/bcr-2019-230543. PubMed PMID: 31366616.
5)

Xue G, Liu P, Xu F, Fang Y, Li Q, Hong B, Xu Y, Liu J, Huang Q. Endovascular Treatment of Ruptured Wide-Necked Anterior Communicating Artery Aneurysms Using a Low-Profile Visualized Intraluminal Support (LVIS) Device. Front Neurol. 2021 Jan 28;11:611875. doi: 10.3389/fneur.2020.611875. PMID: 33584512; PMCID: PMC7876256.

terior communicating artery aneurysm endovascular treatment complications

Cystic brain metastases treatment

Cystic brain metastases treatment

When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decrease the chance of radiation-induced necrosis and provide symptomatic relief from the mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications for improving patient outcomes 1).

Ommaya reservoir implantation during stereotactic cyst aspiration is necessary to prevent fluid reaccumulation, thereby avoiding the need for a second surgical procedure 2).

Flickinger 3) reported that tumors with a cystic component greater than 10 mL did not appear to be effectively controlled by radiosurgery alone. Therefore, it is essential to decrease the volume of the cystic components before treating them with radiosurgery. The combination of cyst aspiration and radiosurgery is one possible method 4) 5) 6) 7) that may be more effective and safer than radiosurgery alone.

Tumor cyst aspiration followed by Gamma Knife radiosurgery (GKRS) for large cystic brain metastases is a reasonable and effective management strategy. However, even with aspiration, the target lesion tends to exceed the dimensions of an ideal target for stereotactic radiosurgery. In this case, the local tumor control rate and the risk of complication might be a critical challenge.

A study aimed to investigate whether fractionated GKRS (f-GKRS) could solve these problems. Between May 2018 and April 2021, eight consecutive patients with nine lesions were treated with f-GKRS in five or ten sessions after cyst aspiration. The aspiration was repeated as needed throughout the treatment course to maintain the cyst size and shape. The patient characteristics, radiologic tumor response, and clinical course were reviewed using medical records. The mean follow-up duration was 10.2 (2-28) months. The mean pre-GKRS volume and maximum diameter were 16.7 (5-55.8) mL and 39.0 (31-79) mm, respectively. The mean tumor volume reduction achieved by aspiration was 55.4%. The tumor volume decreased for all lesions, and symptoms were alleviated in all patients. The median overall survival was 10.0 months, and the estimated 1-year survival rate was 41.7% (95% CI: 10.9-70.8%). The local tumor control rate was 100%. No irradiation-related adverse events were observed. f-GKRS for aspirated cystic brain metastasis is a safe, effective, and less invasive management option for large cystic brain metastases 8).

1)

Kim M, Cheok S, Chung LK, Ung N, Thill K, Voth B, Kwon DH, Kim JH, Kim CJ, Tenn S, Lee P, Yang I. Characteristics and treatments of large cystic brain metastasis: radiosurgery and stereotactic aspiration. Brain Tumor Res Treat. 2015 Apr;3(1):1-7. doi: 10.14791/btrt.2015.3.1.1. Epub 2015 Apr 29. PMID: 25977901; PMCID: PMC4426272.
2)

Lv J, Wu Z, Wang K, Wang Y, Yang S, Han W. Case Report: Clinical and Procedural Implications of Ommaya Reservoir Implantation in Cystic Brain Metastases Followed by Radiosurgery Treatment. Front Surg. 2022 May 16;9:901674. doi: 10.3389/fsurg.2022.901674. PMID: 35651693; PMCID: PMC9149303.
3)

Flickinger JC. Radiotherapy and radiosurgical management of brain metastases. Curr Oncol Rep. 2001 Nov;3(6):484-9. doi: 10.1007/s11912-001-0069-5. PMID: 11595116.
4)

Loeffler JS, Barker FG, Chapman PH. Role of radiosurgery in the management of central nervous system metastases. Cancer Chemother Pharmacol. 1999;43 Suppl:S11-4. doi: 10.1007/s002800051092. PMID: 10357553.
5)

Kim MS, Lee SI, Sim SH. Brain tumors with cysts treated with Gamma Knife radiosurgery: is microsurgery indicated. Stereotact Funct Neurosurg. 1999;72(Suppl 1):38–44.
6)

Niranjan A, Witham T, Kondziolka D, Lunsford LD. The role of stereotactic cyst aspiration for glial and metastatic brain tumors. Can J Neurol Sci. 2000;27:229–235.
7)

Uchino M, Nagao T, Seiki Y, Shibata I, Terao H, Kaneko I. [Radiosurgery for cystic metastatic brain tumor] No Shinkei Geka. 2000;28:417–421.
8)

Noda R, Akabane A, Kawashima M, Oshima A, Tsunoda S, Segawa M, Inoue T. Fractionated Gamma Knife radiosurgery after cyst aspiration for large cystic brain metastases: case series and literature review. Neurosurg Rev. 2022 Jul 14. doi: 10.1007/s10143-022-01835-y. Epub ahead of print. PMID: 35834076.

Delayed cerebral ischemia treatment

Delayed cerebral ischemia treatment

Should We Focus on Blood Pressure or Vasodilatation? 1)

Rescue treatment for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can include induced hypertension (iHTN) and, in refractory cases, endovascular approaches, of which selective, continuous intraarterial nimodipine (IAN) is one variant. The combination of iHTN and IAN can dramatically increase vasopressor demand. In case of unsustainable doses, iHTN is often prioritized over IAN. However, evidence in this regard is largely lacking 2)

Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated 3).

To date, the only drug shown to be efficacious on both the incidence of vasospasm and poor outcome is nimodipine. Given its modest effects, new pharmacological treatments are being developed to prevent and treat DCI 4)

Volume expansion and hypertension

Volume expansion and hypertension are widely used for the hemodynamic management of patients with subarachnoid hemorrhage to prevent delayed cerebral ischemia.

For small, unruptured, unprotected intracranial aneurysms in SAH patients, the frequency of aneurysm rupture during vasopressor-induced hypertension (VIH) therapy is rare. Reynolds et al. do not recommend withholding VIH therapy from these patients 5).

A randomized pilot trial using a 2-way factorial design allocating patients within 72 hours of subarachnoid hemorrhage to either normovolemia (NV) or volume expansion (HV) and simultaneously to conventional (CBP) or augmented blood pressure (ABP) for 10 days. The study endpoints were protocol adherence and retention to follow-up. The quality of endpoints for a larger trial were 6-month modified Rankin Scale score, comprehensive neurobehavioral assessment, delayed cerebral ischemia, new stroke, and discharge disposition.

This pilot study showed adequate feasibility and excellent retention to follow-up. Given the suggestion of possible worse neurobehavioral outcome with ABP, a larger trial to determine the optimal blood pressure management in this patient population is warranted. (ClinTrials.gov NCT01414894.) 6).

Prevention

see Delayed cerebral ischemia prevention.

1)

Sadan O, Akbik F. Treating Delayed Cerebral Ischemia: Should We Focus on Blood Pressure or Vasodilatation? Stroke. 2022 Jun 8:101161STROKEAHA122039800. doi: 10.1161/STROKEAHA.122.039800. Epub ahead of print. PMID: 35674047.
2)

Weiss M, Albanna W, Conzen-Dilger C, Kastenholz N, Seyfried K, Ridwan H, Wiesmann M, Veldeman M, Schmidt TP, Megjhani M, Schulze-Steinen H, Clusmann H, Aries MJH, Park S, Schubert GA. Intraarterial Nimodipine Versus Induced Hypertension for Delayed Cerebral Ischemia: A Modified Treatment Protocol. Stroke. 2022 Jun 8:101161STROKEAHA121038216. doi: 10.1161/STROKEAHA.121.038216. Epub ahead of print. PMID: 35674046.
3)

Francoeur CL, Mayer SA. Management of delayed cerebral ischemia after subarachnoid hemorrhage. Crit Care. 2016 Oct 14;20(1):277. doi: 10.1186/s13054-016-1447-6. PMID: 27737684; PMCID: PMC5064957.
4)

Castanares-Zapatero D, Hantson P. Pharmacological treatment of delayed cerebral ischemia and vasospasm in subarachnoid hemorrhage. Ann Intensive Care. 2011 May 24;1(1):12. doi: 10.1186/2110-5820-1-12. PMID: 21906344; PMCID: PMC3224484.
5)

Reynolds MR, Buckley RT, Indrakanti SS, Turkmani AH, Oh G, Crobeddu E, Fargen KM, El Ahmadieh TY, Naidech AM, Amin-Hanjani S, Lanzino G, Hoh BL, Bendok BR, Zipfel GJ. The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms. J Neurosurg. 2015 Oct;123(4):862-71. doi: 10.3171/2014.12.JNS141201. Epub 2015 Jul 24. PubMed PMID: 26207606.
6)

Togashi K, Joffe AM, Sekhar L, Kim L, Lam A, Yanez D, Broeckel-Elrod JA, Moore A, Deem S, Khandelwal N, Souter MJ, Treggiari MM. Randomized Pilot Trial of Intensive Management of Blood Pressure or Volume Expansion in Subarachnoid Hemorrhage (IMPROVES). Neurosurgery. 2015 Feb;76(2):125-35. doi: 10.1227/NEU.0000000000000592. PubMed PMID: 25549192.

Shunt for Idiopathic normal pressure hydrocephalus treatment

Shunt for Idiopathic normal pressure hydrocephalus treatment

Indications

• Early shunt surgery can significantly improve the clinical symptoms and prognosis of patients with idiopathic normal pressure hydrocephalus (iNPH). • Structural imaging findings have limited predictiveness for the prognosis of patients with iNPH after shunt surgery. • Patients should not be selected for shunt surgery based on only structural imaging findings 1).

Clinical decisions regarding Shunt for Idiopathic normal pressure hydrocephalus treatment should be individualized to each patient, with adequate consideration of the relative risks and benefits, including maximizing a healthy life expectancy 2).

Ventriculoperitoneal shunt for idiopathic normal pressure hydrocephalus

see Ventriculoperitoneal shunt for idiopathic normal pressure hydrocephalus.

Lumboperitoneal shunt for idiopathic normal pressure hydrocephalus

see Lumboperitoneal shunt for idiopathic normal pressure hydrocephalus.

1)

Chen J, He W, Zhang X, Lv M, Zhou X, Yang X, Wei H, Ma H, Li H, Xia J. Value of MRI-based semi-quantitative structural neuroimaging in predicting the prognosis of patients with idiopathic normal pressure hydrocephalus after shunt surgery. Eur Radiol. 2022 Apr 30. doi: 10.1007/s00330-022-08733-3. Epub ahead of print. PMID: 35501572.
2)

Nakajima M, Kuriyama N, Miyajima M, Ogino I, Akiba C, Kawamura K, Kurosawa M, Watanabe Y, Fukushima W, Mori E, Kato T, Sugano H, Tange Y, Karagiozov K, Arai H. Background Risk Factors Associated with Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus: A Nationwide Hospital-Based Survey in Japan. J Alzheimers Dis. 2019 Mar 11. doi: 10.3233/JAD-180955. [Epub ahead of print] PubMed PMID: 30883349.