Update: Internal carotid artery bifurcation aneurysm

Internal carotid artery bifurcation aneurysm

Internal carotid artery bifurcation aneurysms are subtype of internal carotid artery aneurysm.

Epidemiology

Internal carotid artery bifurcation aneurysms represent between 2.4% and 4% of all intracranial aneurysm1) 2)3) 4).

Complications

They frequently rupture at a younger age compared to other intracranial aneurysms 5).

Additionally, the increased hemodynamic stress at this level translates into a higher rate of recurrence compared with aneurysms in other locations6) 7)

Classification

Small

Large

Giant

Projection

Superior

Anterior

Posterior

Treatment

Treatment is therefore recommended since they tend to bleed at a lower age than other aneurysms 8).

The presence of multiple perforators in this area along with the angle of origin often skewed toward the MCA or the anterior cerebral artery primarily can make treatment challenging 9).

Surgical treatment

The surgical treatment of ICA bifurcation aneurysms is particularly challenging, due to their location at the highest point of the ICA and the presence of multiple perforators at this level that may be adherent to the back side of the aneurysm 10)

Endovascular treatment

Endovascular treatment of ICA bifurcation aneurysms is feasible and effective and is associated with high immediate angiographic occlusion rates. However, retreatment rates and procedure-related morbidity and mortality are non-negligible 11).

Periprocedural complications following endovascular treatment of ICA terminus aneurysms are not negligible. Aneurysms at this location are at a high risk of ischemic stroke in the territory of the ipsilateral MCA (either from distal emboli during the procedure or clot formation at the level of the neck with impairment of distal MCA flow), a potential source of serious morbidity and mortality 12) 13) 14).

In the meta-analysis of Morales-Valero et al., perioperative morbidity rates were approximately 4% and mortality rates were 3%. Perioperative stroke was a major contributor to morbidity and mortality, occurring in approximately 3% of patients. Although good long-term neurologic outcome was achieved in 90% of patients regardless of aneurysm rupture status, the periprocedural complication rate reported is not trivial. Particularly worrisome is the procedure-related mortality of 4% for unruptured and 6% for ruptured ICA bifurcation aneurysms. These findings stress the importance of proper patient selection because these aneurysms are often adequately and effectively treatable with surgical clip ligation. The high retreatment rate observed in the meta-analysis and in the own series is similar to that reported for aneurysms located in other bifurcation points 15).

Videos

Case series

2016

Fifty-nine patients with 61 unruptured ICAbifAs were included. Seven aneurysms were treated surgically (11.5 %), 22 underwent endovascular treatment (36 %), and 32 were managed conservatively (52.5 %). In the surgical group, short- and long-term complete aneurysm occlusion rates were 100 % with no cases of perioperative or long-term permanent morbidity or treatment-related mortality. In the endovascular group, two patients (11.7 %) with giant aneurysms had perioperative thromboembolic events with transient morbidity. There was one case of aneurysm rupture at follow-up in a giant aneurysm treated with partial coil embolization. Complete/near-complete occlusion rates were 63 %. There was one case of aneurysm rupture after 114 aneurysm-years of follow-up in the conservative management group (0.89 %/year), but no ruptures were observed in small aneurysms selected for conservative management.

Unruptured small ICAbifAs have a benign natural history. In patients selected for treatment, excellent results can be achieved in the vast majority of patients with judicious use of endovascular and surgical therapy 16).

2015

A total of 58 patients with ICA bifurcation aneurysms were treated. By interdisciplinary consensus, 30 aneurysms were assigned for coiling and 28 for clipping. Patients who underwent surgical clipping were younger and had larger aneurysms. More patients were assigned to coiling if their aneurysms originated only from the ICA bifurcation or projected superiorly. For the combined angiographic endpoint, complete and nearly complete occlusion (Raymond-Roy I + II), similar rates of 96% (coiling) or 100% (clipping) could be achieved. Raymond-Roy I occlusion occurred more often after clipping (79% vs 41% coiling). Follow-up of the endovascular group showed minor recanalization of the aneurysm neck (Raymond-Roy II) in 42%. One patient (4%) showed a major recanalization (Raymond-Roy III) and needed re-treatment. For incidental findings, no bleeding complications or new persistent neurological deficits occurred during follow-up.

Treatment of ICA bifurcation aneurysms after interdisciplinary assignment to clipping or coiling is effective and safe. Despite significantly more minor recanalizations after coiling, the re-treatment rate was very low, and no bleeding was observed during follow-up. Multivariate analysis revealed that origin only from the ICA bifurcation was an independent predictor of aneurysm recanalization after endovascular treatment 17).

2007

Internal carotid artery (ICA) bifurcation aneurysms are relatively uncommon and frequently rupture at a younger age compared to other intracranial aneurysms.

Gupta et al treated a total of 999 patients for intracranial aneurysms, of whom 89 (8.9%) had ICA bifurcation aneurysms, and 42 of the 89 patients were 30 years of age or younger. The study analyzed the clinical records of 70 patients with ICA bifurcation aneurysms treated from mid 1997 to mid 2003. Multiple aneurysms were present in 15 patients. Digital subtraction angiography films were studied in 55 patients to identify vasospasm and aneurysm projection. The aneurysm projected superiorly in most of these patients (37/55, 67.3%).

They preferred to minimize frontal lobe retraction, so widely opened the sylvian fissure to approach the ICA bifurcation and aneurysm neck. Elective temporary clipping was employed before the final dissection and permanent clip application. Vasospasm was present in 24 (43.6%) of 55 patients. Forty-eight (68.6%) of the 70 patients had good outcome, 14 (20%) had poor outcome, and eight (11.4%) died. Patients with ICA bifurcation aneurysms tend to bleed at a much younger age compared to those with other intracranial aneurysms. Wide opening of the sylvian fissure and elective temporary clipping of the ICA reduces the risk of intraoperative rupture and perforator injury. Mortality was mainly due to poor clinical grade and intraoperative premature aneurysm rupture 18).

2002

A series of 25 patients treated by clipping under the operating microscope are analyzed and compared with previous cases. Twenty-five patients, 11 men and 14 women (mean age 51 years), were treated by the same neurosurgeon. Seventeen patients presented with subarachnoid hemorrhage (Hunt & Kosnik Grade I in three, II in five, III in two, IV in seven), five with unruptured ICA bifurcation aneurysms, and three with unruptured ICA bifurcation aneurysms but another ruptured aneurysm. There were 23 small, one large, and one giant ICA bifurcation aneurysms. The projection was superior in 12, anterior in seven, and posterior in six cases. Pterional approach was employed for all cases. Outcomes were evaluated at discharge with the Glasgow Outcome Scale. Favorable outcomes (good recovery (GR) and moderate disability (MD)) were obtained in ten of 17 patients with ruptured ICA bifurcation aneurysm. Favorable outcomes were significantly greater in Grades I and II (three in I, four in II) than in Grades III and IV (one in III, two in IV; P=0.0498). Seven of eight patients with unruptured ICA bifurcation aneurysm had favorable outcomes. Temporary clipping and projection of the aneurysm did not affect the outcome. Causative factors of unfavorable outcomes were primary brain damage in cases of small and large aneurysms and perforator damage in the case of giant aneurysm. Poor clinical grade and vasospasm are the causative factors of poor outcome in patients with ruptured ICA bifurcation aneurysm. Preservation of perforators is crucial in cases of giant aneurysm. Clipping of unruptured ICA bifurcation aneurysms is recommended since they tend to bleed at a lower age than other aneurysms 19).

Case reports

2015

A 70-year-old man with progressive visual disturbances, left superior quadrantanopsia, and right-sided papilledema underwent imaging that demonstrated a right internal carotid artery (ICA) terminus aneurysm with third-ventricle mass effect and ipsilateral optic nerve and chiasm compression. We performed a right modified orbitozygomatic craniotomy, with proximal control and dissection of the aneurysm and small perforator arteries. Temporary ICA and anterior cerebral artery (ACA) clips allowed placement of a large curved permanent clip, reconstructing the ICA bifurcation and maintaining adequate patency of the ACA and middle cerebral artery. Complete aneurysm obliteration was confirmed by intraoperative indocyanine green angiography and postoperative CT angiography. The video can be found here: http://youtu.be/5WEEgmA-g2A20).


A 64-year-old woman, with visual deficit, harboring a large wide-necked aneurysm located at the junction between left internal carotid artery and left A1 segment of anterior cerebral artery, was submitted to endovascular treatment. As she had pre-existing occlusion of left internal carotid, approach from the contralateral internal carotid was used to advance the pipeline embolization device through the anterior communicating artery and place the flow diverter horizontally across the neck (from M1 to A1). Coil embolization was also performed through a microcatheter navigated via posterior communicating artery. The intervention was uneventful, with total aneurysm occlusion. Patient presented with visual improvement on follow-up.

Horizontal deployment of pipeline embolization device appears to be an acceptable and feasible alternative to treat internal carotid bifurcation aneurysms. Long-term follow-up and a greater number of cases are mandatory to establish the safety of this strategy 21).

2009

A surgical case of an eleven year old boy with excellent outcome is reported, with a subsequent review on the subject. Patients may present with classical subarachnoidal hemorrhage, but also with compressive signs with bigger and unruptured lesions. Initial management of these cases is basically the same of older patients, considering their age, weight and special intensive care for infants 22).

2006

A 58-year-old hypertensive woman presenting with mild headaches underwent computed tomography, which showed a nonruptured aneurysm of the left internal carotid artery. She subsequently underwent cerebral angiography, confirming that the aneurysm was located at the left terminal carotid segment with a wide neck. INTERVENTION: Using a cross-over approach from the contralateral internal carotid artery, a new self-expandable stent was advanced through the anterior communicating artery and placed horizontally across the aneurysm neck. Aneurysm occlusion was performed by subsequent trans-stent catheterization of the aneurysm and coil packing.

Successful stent placement allowed subtotal coil occlusion of the aneurysm with a good anatomic and clinical result. No complications were encountered. The new self-expandable stent is a highly flexible, low-profile device that can be safely navigated through tortuous intracranial vessels even in a crossover technique. Its radial force and closed cell design is suitable for stent-assisted coiling and may be superior to stents with an open cell design 23).

1)

Sakamoto S, Ohba S, Shibukawa M, et al. Characteristics of aneurysms of the internal carotid artery bifurcation. Acta Neurochir (Wien) 2006;148:139 –43, discussion 143
2) , 8) , 9) , 19)

Miyazawa N, Nukui H, Horikoshi T, Yagishita T, Sugita M, Kanemaru K. Surgical management of aneurysms of the bifurcation of the internal carotid artery. Clin Neurol Neurosurg. 2002 May;104(2):103-14. PubMed PMID: 11932039.
3) , 10)

Lehecka M, Dashti R, Romani R, et al. Microneurosurgical management of internal carotid artery bifurcation aneurysms. Surg Neurol 2009;71:649 –67
4) , 6) , 12)

van Rooij WJ, Sluzewski M, Beute GN. Internal carotid bifurcation aneurysms: frequency, angiographic anatomy and results of coiling in 50 aneurysms. Neuroradiology 2008;50:583–87
5) , 18)

Gupta SK, Khosla VK, Chhabra R, Mohindra S, Bapuraj JR, Khandelwal N, Mukherjee KK, Tewari MK, Pathak A, Mathuriya SN. Internal carotid artery bifurcation aneurysms: surgical experience. Neurol Med Chir (Tokyo). 2007 Apr;47(4):153-7; discussion 157-8. PubMed PMID: 17457018.
7)

Ingebrigtsen T, Morgan MK, Faulder K, et al. Bifurcation geometry and the presence of cerebral artery aneurysms. J Neurosurg 2004;101:108 –13
11) , 15)

Morales-Valero SF, Brinjikji W, Murad MH, Wald JT, Lanzino G. Endovascular treatment of internal carotid artery bifurcation aneurysms: a single-center experience and a systematic review and meta-analysis. AJNR Am J Neuroradiol. 2014 Oct;35(10):1948-53. doi: 10.3174/ajnr.A3992. Epub 2014 Jun 5. Review. PubMed PMID: 24904050.
13)

Uemura A, Musacchio M, Cardoso M, et al. Internal carotid bifurcation aneurysms: anatomical features and outcome of endovascular treatment. Neuroradiol J 2008;21:574 –78
14)

Oishi H, Yamamoto M, Nonaka S, et al. Endovascular therapy of internal carotid artery bifurcation aneurysms. J Neurointerv Surg 2013;5:400 –04
16)

La Pira B, Brinjikji W, Burrows AM, Cloft HJ, Vine RL, Lanzino G. Unruptured internal carotid artery bifurcation aneurysms: general features and overall results after modern treatment. Acta Neurochir (Wien). 2016 Nov;158(11):2053-2059. PubMed PMID: 27644699.
17)

Konczalla J, Platz J, Brawanski N, Güresir E, Lescher S, Senft C, du Mesnil de Rochemont R, Berkefeld J, Seifert V. Endovascular and surgical treatment of internal carotid bifurcation aneurysms: comparison of results, outcome, and mid-term follow-up. Neurosurgery. 2015 May;76(5):540-50; discussion 550-1. doi: 10.1227/NEU.0000000000000672. PubMed PMID: 25635884.
20)

Rangel-Castilla L, Spetzler RF. Microsurgical management of a large ICA bifurcation aneurysm. Neurosurg Focus. 2015 Jul;39 Video Suppl 1:V18. doi: 10.3171/2015.7.FocusVid.14646. PubMed PMID: 26132616.
21)

Trivelato FP, Araújo JF, Salles Rezende MT, Ulhôa AC. A Novel Configuration of Pipeline Embolization Device for Internal Carotid Bifurcation Region Aneurysms: Horizontal Deployment. Clin Neuroradiol. 2015 Jun 6. [Epub ahead of print] PubMed PMID: 26047919.
22)

Meireles Borba A, Santana Pereira RS, Godinho A, Casulari LA. Internal carotid bifurcation aneurysm in childhood: a case report and literature review. J Neurosurg Sci. 2009 Sep;53(3):131-6. Review. PubMed PMID: 20075826.
23)

Benndorf G, Klucznik RP, Meyer D, Strother CM, Mawad ME. “Cross-over” technique for horizontal stenting of an internal carotid bifurcation aneurysm using a new self-expandable stent: technical case report. Neurosurgery. 2006 Feb;58(1 Suppl):ONS-E172; discussion ONS-E172. PubMed PMID: 16462622.

Update: Chronic subdural hematoma recurrence

Chronic subdural hematoma recurrence

Epidemiology

Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques twist drill craniostomy (TDC), burr hole craniostomy, craniotomy range from 5% to 30%. 1)

Risk factors

Chon et al. shown that postoperative midline shifting (≥5 mm), diabetes mellitus, preoperative seizure, preoperative width of hematoma (≥20 mm), and anticoagulant therapy were independent predictors of the recurrence of chronic subdural hematoma. According to internal architecture of hematoma, the rate of recurrence was significantly lower in the homogeneous and the trabecular type than the laminar and separated type 2).

The recurrence rate of chronic subdural hematoma cSDH seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the hematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclooxygenase-2 (COX-2).


Antiplatelet therapy

Antiplatelet therapy significantly influences the recurrence of CSDH 3).

Pneumocephalus

Remaining pneumocephalus is seen as an approved factor of recurrence 4) 5).

Septation

Jack et al.found a 12% reoperation rate. CSDH septation (seen on computed tomogram scan) was found to be an independent risk factor for recurrence requiring reoperation (p=0.04). Larger post-operative subdural haematoma volume was also significantly associated with requiring a second drainage procedure (p<0.001). Independent risk factors of larger post-operative haematoma volume included septations within a CSDH (p<0.01), increased pre-operative haematoma volume (p<0.01), and a greater amount of parenchymal atrophy (p=0.04). A simple scoring system for quantifying recurrence risk was created and validated based on patient age (< or ≥80 years), haematoma volume (< or ≥160cc), and presence of septations within the subdural collection (yes or no).

Septations within CSDHs are associated with larger post-operative residual haematoma collections requiring repeat drainage. When septations are clearly visible within a CSDH, craniotomy might be more suitable as a primary procedure as it allows greater access to a septated subdural collection. The proposed scoring system combining haematoma volume, age, and presence of septations might be useful in identifying patients at higher risk for recurrence 6).

Membranectomy

Opening the internal hematoma membrane does not alter the rate of patients requiring revision surgery and the number of patients showing a marked residual hematoma six weeks after evacuation of a CSDH 7).

In the study of Lee et al, an extended surgical approach with partial membranectomy has no advantages regarding the rate of reoperation and the outcome. As initial treatment, burr-hole drainage with irrigation of the hematoma cavity and closed-system drainage is recommended. Extended craniotomy with membranectomy is now reserved for instances of acute rebleeding with solid hematoma 8).

Diabetes

Surgeons should consider informing patients with diabetes mellitus that this comorbidity is associated with an increased likelihood of recurrence

9) 10) 11).


Balser et al. report 11% recurrence, which included individuals who recurred as late as 3 years after initial diagnosis 12).

Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the ‘self-resolution’ period can be used as significantly radiological predictors of recurrence 13).

A structural equation model showed a significant association between increased antiinflammatory activity in hematoma fluid samples and a lower risk of recurrence, but this relationship was not statistically significant in venous blood samples. Moreover, these findings indicate that anti-inflammatory activities in the hematoma may play a role in the risk of a recurrence of CSDH 14).

Irrigation with artificial cerebrospinal fluid (ACF) decreased the rate of CSDH recurrence 15).

Treatment

There is no definite operative procedure for patients with intractable chronic subdural hematoma (CSDH).

Most recurrent hematomas are managed successfully with burr hole craniostomies with postoperative closed-system drainage. Refractory hematomas may be managed with a variety of techniques, including craniotomy or subdural-peritoneal shunt placement 16).

Although many studies have reported risk factors or treatments in efforts to prevent recurrence, those have focused on single recurrence, and little cumulative data is available to analyze refractory CSDH.

Matsumoto et al. defined refractory CSDH as ≥2 recurrences, then analyzed and compared clinical factors between patients with single recurrence and those with refractory CSDH in a cohort study, to clarify whether patients with refractory CSDH experience different or more risk factors than patients with single recurrence, and whether burr-hole irrigation with closed-system drainage reduces refractory CSDH.

Seventy-five patients had at least one recurrence, with single recurrence in 62 patients and ≥2 recurrences in 13 patients. In comparing clinical characteristics, patients with refractory CSDH were significantly younger (P=0.04) and showed shorter interval to first recurrence (P<0.001). Organized CSDH was also significantly associated with refractory CSDH (P=0.02). Multivariate logistic regression analysis identified first recurrence interval <1 month (OR 6.66, P<0.001) and age <71 years (OR 4.16, P<0.001) as independent risk factors for refractory CSDH. On the other hand, burr-hole irrigation with closed-system drainage did not reduce refractory CSDH.

When patients with risk factors for refractory CSDH experience recurrence, alternative surgical procedures may be considered as the second surgery, because burr-hole irrigation with closed-system drainage did not reduce refractory CSDH 17).

Implantation of a reservoir 18) 19) 20).

Subdural-peritoneal shunt 21).

Middle meningeal artery embolization

Embolization of the MMA is effective for refractory CSDH or CSDH patients with a risk of recurrence, and is considered an effective therapeutic method to stop hematoma enlargement and promote resolution 22) 23) 24) 25) 26) 27).

A pilot study indicated that perioperative middle meningeal artery (MMA) embolization could be offered as the least invasive and most effectual means of treatment for resistant patients of CSDHs with 1 or more recurrences 28).

Chihara et al. have treated three cases of CSDH with MMA embolization to date, but there was a postoperative recurrence in one patient, which required a craniotomy for hematoma removal and capsulectomy. MMA embolization blocks the blood supply from the dura to the hematoma outer membrane in order to prevent recurrences of refractory CSDH. Histopathologic examination of the outer membrane of the hematoma excised during craniotomy showed foreign-body giant cells and neovascular proliferation associated with embolization. Because part of the hematoma was organized in this case, the CSDH did not resolve when the MMA was occluded, and the development of new collateral pathways in the hematoma outer membrane probably contributed to the recurrence. Therefore, in CSDH with some organized hematoma, MMA embolization may not be effective. Magnetic resonance imaging (MRI) should be performed in these patients before embolization 29).

Case series

2016

Chronic subdural hematomas (cSDHs) have shown an increasing incidence in an ageing population over the last 20 years, while unacceptable recurrence rates of up to 30 % persist. The chronic subdural hematoma recurrence rate seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the haematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclooxygenase-2 (COX 2). With this investigator-initiated trial (IIT) it was thought to diminish the recurrence rate of operated-on cSDHs by administering a selective COX-2 inhibitor (Celecoxib) over 4 weeks’ time postoperatively in comparison to a control group.

The thesis of risk reduction of cSDH recurrence in COX-2-inhibited patients was to be determined in a prospective, randomised, two-armed, open phase-II/III study with inclusion of 180 patients over a 2-year time period in four German university hospitals. The treated- and untreated-patient data were to be analysed by Fisher’s exact test (significance level of alpha, 0.05 [two-sided]).

After screening of 246 patients from January 2009 to April 2010, the study had to be terminated prematurely as only 23 patients (9.3 %) could be enrolled because of on-going non-steroid anti-rheumatic (NSAR) drug treatment or contraindication to Celecoxib medication. In the study population, 13 patients were treated in the control group (six women, seven men; average age 66.8 years; one adverse event (AE)/serious adverse event (SAE) needing one re-operation because of progressive cSDH (7.7 %); ten patients were treated in the treatment group (one woman, nine men; average age 64.7 years; five AEs/SAEs needing two re-operations because of one progressive cSDH and one wound infection [20 %]). Significance levels are obsolete because of insufficient patient numbers.

The theoretical advantage of COX-2 inhibition in the recurrent cSDH could not be transferred into the treatment of German cSDH patients as 66.6 % of the patients showed strict contraindications for Celecoxib. Furthermore, 55 % of the patients were already treated with some kind of COX-2 inhibition and, nevertheless, developed cSDH. Thus, although conceptually appealing, an anti-angiogenic therapy with COX-2 inhibitors for cSDH could not be realised in this patient population due to the high prevalence of comorbidities excluding the administration of COX2 inhibitors 30).

2010

Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques twist drill craniostomy (TDC), burr holecraniostomy, craniotomy range from 5% to 30%. Use of drain has improved recurrence rates when used with burr-hole craniostomy. Now, we analyze predictors of recurrence of TDC with drain.

Three hundred twelve consecutive patients with CSDH have been studied in a retrospective study. Operative technique in all patients consisted in TDC with drain. Data recorded included any associated comorbidity. Radiologic measures of the CSDH before and after the procedure were studied. Clinical evaluation included Modified Rankin Scale, Glasgow Coma Scale (GCS), and neurological deficits. Two groups were compared: recurrence group and nonrecurrence group. Follow-up was for at least 1 year.

Twelve percent experienced recurrence. Preoperative CSDH width, preoperative midline shift, postoperative midline width, postoperative CSDH width, and residual CSDH 1 month later were significantly associated with CSDH recurrence. The logistic regression model for the multivariate analysis revealed that postoperative midline shift and postoperative neurological deficit were significantly associated with CSDH recurrence. The duration of treatment with dexamethasone was found not to be related with recurrence. Mortality before hospital discharge was 1%. Hospital stay was 2.5 days.

TDC with drain has similar results in recurrence rates, morbidity, mortality, and outcome as other techniques as burr-hole craniostomy with drain. Preoperative and postoperative hematoma width and midline shift are independent predictors of recurrence. Brain re-expansion and time of drain maintenance are important factors related with recurrence of CSDH. Future CSDH reservoirs must avoid negative pressure and sudden pressure changes inside the whole closed drain system 31).

Case reports

2016

Mewada et al. report a case with right hemiparesis and aphasia 1 month after a fall from a bicycle. Computed tomography scan of the head showed left chronic subdural hematoma, which was evacuated by burr-hole drainage. The postoperative course was complicated by reaccumulation within short period of time. On superselective digital subtraction angiography of MMA, iatrogenic dAVF was found on left side. We embolized successfully it using n-butyl cyanoacrylate after a third irrigation. No reaccumulation found in the postoperative period or at last follow-up. They proposed a treatment protocol based on the own experience and literature review.

Refractory chronic subdural hematoma with reaccumulation within a short interval should be subjected to digital subtraction angiography of the MMA. Embolization of ipsilateral MMA is safe, effective, and a useful option for the treatment of iatrogenic dAVF and resolution of hematoma 32).


An 85-year-old male presented with left CSDH, which recurred five times. The hematoma was irrigated and drained through a left frontal burr hole during the first to third surgery and through a left parietal burr hole during the fourth and fifth surgery. The hematoma had no septation and was well-evacuated during each surgery. Antiplatelet therapy for preventing ischemic heart disease was stopped after the second surgery, the hematoma cavity was irrigated with artificial cerebrospinal fluid at the third surgery, and the direction of the drainage tube was changed to reduce the postoperative subdural air collection at the fourth surgery. However, none of these interventions was effective. He was successfully treated by fibrin glue injection into the hematoma cavity after the fifth surgery.

This procedure may be effective for refractory CSDH in elderly patients 33).


A 67-year-old man with dural arteriovenous fistula (AVF) presenting as a non-traumatic chronic subdural hematoma (CSDH). This previously healthy patient was hospitalized due to progressive headache with subacute onset. He underwent burr-hole surgery twice for evacuating the left CSDH that was thickest at the posterior temporal area. The operative procedure and finding was not extraordinary, but subdural hematoma slowly progressed for days following the revision surgery. After investigation by super-selective external carotid angiography, a dural AVF found near the transverse-sigmoid sinus was diagnosed. Dural AVF was completely occluded with trans-arterial injecting polyvinyl alchol particles into the petrosquamosal branch of the middle meningeal artery. The patient showed a good neurological outcome with no additional intervention. Brain surgeons have to consider the possibility of dural AVF and perform cerebral angiogram if necessary when they manage the cases that have a spontaneously occurred and repeatedly recurring CSDH 34).

2007

Spontaneous intracranial hypotension (SIH) is reported to cause chronic subdural hematoma (SDH), however diagnosis of SIH in patients with SDH is not always easy.

Takahashi et al. report a case of chronic SDH refractory to repeated drainage, which was attributed to SIH. A forty-five-year-old man who had been suffering from orthostatic headache for one month was admitted to our hospital presenting with unconsciousness and hemiparesis. CT on admission revealed a chronic subdural hematoma, which was successfully treated once with subdural drainage. However, the patient fell into unconscious again with recurrence of the hematoma within several days. After two more sessions of drainage, SIH due to cerebrospinal fluid leakage was diagnosed with spinal magnetic resonance imaging (MRI) and radionuclide cisternography. Spinal MRI demonstrated abnormal fluid accumulation in the thoracic epidural space, and the radionuclide cisternogram showed early excretion of tracer into urine as well as absence of intracranial tracer filling. After treatment with epidural blood patching, the hematoma rapidly disappeared and he was discharged without symptoms. In the treatment of chronic SDH, especially in young to middle aged patient without preceding trauma or hematological disorders, physicians should pay attention to underlying SIH to avoid multiple surgery. MRI of the spine as well as radionuclide cisternography is useful in evaluation of this condition 35).

1) , 31)

Escosa Baé M, Wessling H, Salca HC, de Las Heras Echeverría P. Use of twist-drill craniostomy with drain in evacuation of chronic subdural hematomas: independent predictors of recurrence. Acta Neurochir (Wien). 2011 May;153(5):1097-103. doi: 10.1007/s00701-010-0903-3. Epub 2010 Dec 31. PubMed PMID: 21193935.

2)

Chon KH, Lee JM, Koh EJ, Choi HY. Independent predictors for recurrence of chronic subdural hematoma. Acta Neurochir (Wien). 2012 Sep;154(9):1541-8. doi: 10.1007/s00701-012-1399-9. Epub 2012 Jun 1. PubMed PMID: 22653496.

3)

Wada M, Yamakami I, Higuchi Y, Tanaka M, Suda S, Ono J, Saeki N. Influence of antiplatelet therapy on postoperative recurrence of chronic subdural hematoma: a multicenter retrospective study in 719 patients. Clin Neurol Neurosurg. 2014 May;120:49-54. doi: 10.1016/j.clineuro.2014.02.007. Epub 2014 Feb 24. PubMed PMID: 24731576.

4)

Mori K, Maeda M (2001) Surgical treatment of chronic subdural hematoma in 500 consecutive cases: clinical characteristics, surgical outcome, complications, and recurrence rate. Neurol Med Chir (Tokyo) 41:371–381

5)

Stanišić M, Hald J, Rasmussen IA, Pripp AH, Ivanović J, Kolstad F, Sundseth J, Züchner M, Lindegaard KF (2013) Volume and densities of chronic subdural haematoma obtained from CT imaging as predictors of postoperative recurrence: a prospective study of 107 operated patients. Acta Neurochir 155:323–333

6)

Jack A, O’Kelly C, McDougall C, Max Findlay J. Predicting Recurrence after Chronic Subdural Haematoma Drainage. Can J Neurol Sci. 2015 Jan 5:1-6. [Epub ahead of print] PubMed PMID: 25557536.

7)

Unterhofer C, Freyschlag CF, Thomé C, Ortler M. Opening the Internal Hematoma Membrane does not Alter the Recurrence Rate of Chronic Subdural Hematomas – A Prospective Randomized Trial. World Neurosurg. 2016 May 2. pii: S1878-8750(16)30210-8. doi: 10.1016/j.wneu.2016.04.081. [Epub ahead of print] PubMed PMID: 27150644.

8)

Lee JY, Ebel H, Ernestus RI, Klug N. Various surgical treatments of chronic subdural hematoma and outcome in 172 patients: is membranectomy necessary? Surg Neurol. 2004 Jun;61(6):523-7; discussion 527-8. PubMed PMID: 15165784.

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Matsumoto K, Akagi K, Abekura M, Ryujin H, Ohkawa M, Iwasa N, Akiyama C. Recurrence factors for chronic subdural hematomas after burr-hole craniostomy and closed system drainage. Neurol Res. 1999 Apr;21(3):277-80. PubMed PMID: 10319336.

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Yamamoto H, Hirashima Y, Hamada H, Hayashi N, Origasa H, Endo S. Independent predictors of recurrence of chronic subdural hematoma: results of multivariate analysis performed using a logistic regression model. J Neurosurg. 2003 Jun;98(6):1217-21. PubMed PMID: 12816267.

11)

Pang CH, Lee SE, Kim CH, Kim JE, Kang HS, Park CK, Paek SH, Kim CH, Jahng TA, Kim JW, Kim YH, Kim DG, Chung CK, Jung HW, Yoo H. Acute intracranial bleeding and recurrence after bur hole craniostomy for chronic subdural hematoma. J Neurosurg. 2015 Jul;123(1):65-74. doi: 10.3171/2014.12.JNS141189. Epub 2015 Feb 13. PubMed PMID: 25679282.

12)

Balser D, Rodgers SD, Johnson B, Shi C, Tabak E, Samadani U. Evolving management of symptomatic chronic subdural hematoma: experience of a single institution and review of the literature. Neurol Res. 2013 Apr;35(3):233-42. doi: 10.1179/1743132813Y.0000000166. Review. PubMed PMID: 23485050.

13)

Xu FF, Chen JH, Leung GK, Hao SY, Xu L, Hou ZG, Mao X, Shi GZ, Li JS, Liu BY. Quantitative computer tomography analysis of post-operative subdural fluid volume predicts recurrence of chronic subdural haematoma. Brain Inj. 2014;28(8):1121-6. doi: 10.3109/02699052.2014.910702. Epub 2014 May 6. PubMed PMID: 24801643.

14)

Pripp AH, Stanišić M. The Correlation between Pro- and Anti-Inflammatory Cytokines in Chronic Subdural Hematoma Patients Assessed with Factor Analysis. PLoS One. 2014 Feb 27;9(2):e90149. doi: 10.1371/journal.pone.0090149. eCollection 2014. PubMed PMID: 24587250.

15)

Adachi A, Higuchi Y, Fujikawa A, Machida T, Sueyoshi S, Harigaya K, Ono J, Saeki N. Risk factors in chronic subdural hematoma: comparison of irrigation with artificial cerebrospinal fluid and normal saline in a cohort analysis. PLoS One. 2014 Aug 4;9(8):e103703. doi: 10.1371/journal.pone.0103703. eCollection 2014. PubMed PMID: 25089621; PubMed Central PMCID: PMC4121178.

16)

Desai VR, Scranton RA, Britz GW. Management of Recurrent Subdural Hematomas. Neurosurg Clin N Am. 2017 Apr;28(2):279-286. doi: 10.1016/j.nec.2016.11.010. Epub 2017 Jan 4. Review. PubMed PMID: 28325462.

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Matsumoto H, Hanayama H, Okada T, Sakurai Y, Minami H, Masuda A, Tominaga S, Miyaji K, Yamaura I, Yoshida Y, Yoshida K. Clinical investigation of refractory chronic subdural hematoma: a comparison of clinical factors between single and repeated recurrences. World Neurosurg. 2017 Aug 24. pii: S1878-8750(17)31402-X. doi: 10.1016/j.wneu.2017.08.101. [Epub ahead of print] PubMed PMID: 28844917.

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Sato M, Iwatsuki K, Akiyama C, Masana Y, Yoshimine T, Hayakawa T. [Use of Ommaya CSF reservoir for refractory chronic subdural hematoma]. No Shinkei Geka. 1999 Apr;27(4):323-8. Japanese. PubMed PMID: 10347846.

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Sato M, Iwatsuki K, Akiyama C, Kumura E, Yoshimine T. Implantation of a reservoir for refractory chronic subdural hematoma. Neurosurgery. 2001 Jun;48(6):1297-301. PubMed PMID: 11383733.

20)

Laumer R. Implantation of a reservoir for refractory chronic subdural hematoma. Neurosurgery. 2002 Mar;50(3):672. PubMed PMID: 11841742.

21)

Misra M, Salazar JL, Bloom DM. Subdural-peritoneal shunt: treatment for bilateral chronic subdural hematoma. Surg Neurol. 1996 Oct;46(4):378-83. PubMed PMID: 8876720.

22)

Mandai S, Sakurai M, Matsumoto Y. Middle meningeal artery embolization for refractory chronic subdural hematoma. Case report. J Neurosurg. 2000 Oct;93(4):686-8. PubMed PMID: 11014549.

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Takahashi K, Muraoka K, Sugiura T, Maeda Y, Mandai S, Gohda Y, Kawauchi M, Matsumoto Y. [Middle meningeal artery embolization for refractory chronic subdural hematoma: 3 case reports]. No Shinkei Geka. 2002 May;30(5):535-9. Japanese. PubMed PMID: 11993178.

24)

Hirai S, Ono J, Odaki M, Serizawa T, Nagano O. Embolization of the Middle Meningeal Artery for Refractory Chronic Subdural Haematoma. Usefulness for Patients under Anticoagulant Therapy. Interv Neuroradiol. 2004 Dec 24;10 Suppl 2:101-4. Epub 2008 May 15. PubMed PMID: 20587257; PubMed Central PMCID: PMC3522210.

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Tsukamoto Y, Oishi M, Shinbo J, Fujii Y. Transarterial embolisation for refractory bilateral chronic subdural hematomas in a case with dentatorubral-pallidoluysian atrophy. Acta Neurochir (Wien). 2011 May;153(5):1145-7. doi: 10.1007/s00701-010-0891-3. Epub 2010 Dec 2. PubMed PMID: 21125409.

26)

Mino M, Nishimura S, Hori E, Kohama M, Yonezawa S, Midorikawa H, Kaimori M, Tanaka T, Nishijima M. Efficacy of middle meningeal artery embolization in the treatment of refractory chronic subdural hematoma. Surg Neurol Int. 2010 Dec 13;1:78. doi: 10.4103/2152-7806.73801. PubMed PMID: 21206540; PubMed Central PMCID: PMC3011107.

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Hashimoto T, Ohashi T, Watanabe D, Koyama S, Namatame H, Izawa H, Haraoka R, Okada H, Ichimasu N, Akimoto J, Haraoka J. Usefulness of embolization of the middle meningeal artery for refractory chronic subdural hematomas. Surg Neurol Int. 2013 Aug 19;4:104. doi: 10.4103/2152-7806.116679. eCollection 2013. PubMed PMID: 24032079; PubMed Central PMCID: PMC3766342.

28)

Kim E. Embolization Therapy for Refractory Hemorrhage in Patients with Chronic Subdural Hematomas. World Neurosurg. 2017 May;101:520-527. doi: 10.1016/j.wneu.2017.02.070. Epub 2017 Feb 27. PubMed PMID: 28249828.

29)

Chihara H, Imamura H, Ogura T, Adachi H, Imai Y, Sakai N. Recurrence of a Refractory Chronic Subdural Hematoma after Middle Meningeal Artery Embolization That Required Craniotomy. NMC Case Rep J. 2014 May 9;1(1):1-5. doi: 10.2176/nmccrj.2013-0343. eCollection 2014 Oct. PubMed PMID: 28663942; PubMed Central PMCID: PMC5364934.

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Schaumann A, Klene W, Rosenstengel C, Ringel F, Tüttenberg J, Vajkoczy P. COXIBRAIN: results of the prospective, randomised, phase II/III study for the selective COX-2 inhibition in chronic subdural haematoma patients. Acta Neurochir (Wien). 2016 Nov;158(11):2039-2044. PubMed PMID: 27605230.

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Mewada T, Ohshima T, Yamamoto T, Goto S, Kato Y. Usefulness of Embolization for Iatrogenic Dural Arteriovenous Fistula Associated with Recurrent Chronic Subdural Hematoma: A Case Report and Literature Review. World Neurosurg. 2016 Aug;92:584.e7-584.e10. doi: 10.1016/j.wneu.2016.05.042. Epub 2016 May 27. PubMed PMID: 27241087.

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Watanabe S, Amagasaki K, Shono N, Nakaguchi H. Fibrin glue injection into the hematoma cavity for refractory chronic subdural hematoma: A case report. Surg Neurol Int. 2016 Nov 21;7(Suppl 37):S876-S879. doi: 10.4103/2152-7806.194498. eCollection 2016. PubMed PMID: 27999712; PubMed Central PMCID: PMC5154205.

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Kim E. Refractory Spontaneous Chronic Subdural Hematoma: A Rare Presentation of an Intracranial Arteriovenous Fistula. J Cerebrovasc Endovasc Neurosurg. 2016 Dec;18(4):373-378. doi: 10.7461/jcen.2016.18.4.373. Epub 2016 Dec 31. PubMed PMID: 28184348; PubMed Central PMCID: PMC5298980.

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Takahashi T, Senbokuya N, Horikoshi T, Sato E, Nukui H, Kinouchi H. [Refractory chronic subdural hematoma due to spontaneous intracranial hypotension]. No Shinkei Geka. 2007 Aug;35(8):799-806. Japanese. PubMed PMID: 17695779.

Update: Double level isthmic spondylolisthesis

Double level isthmic spondylolisthesis

Isthmic spondylolisthesis, which is demonstrated in 4%-6% of the general population, is one of the most common types of spondylolisthesis. However, double-level isthmic spondylolisthesis is extremely rare. Only a few reports have examined the outcomes of surgical treatment of double-level spondylolisthesis.

Reviews

Between 2004 and 2014, thirty-two patients with double-level isthmic spondylolisthesis who underwent posterior lumbar interbody fusion (PLIF) with autogenous bone chips were reviewed retrospectively. The clinical outcomes were measured by VAS (Visual analog scale) and JOA(Japanese Orthopaedic Association) score.

At an average follow-up of 2.8 years, the mean score on the VAS of back pain and sciatica decreased from 6.48 and 4.26 points preoperatively to 1.82 and 1.10 points at final follow-up, respectively. The average JOA score improved from 13.8±3.1 preoperative to 25.6±1.3 (range, 17-28) points postoperative. The average recovery rate was 77.6%. The good and excellent rate was 84.3% (27/32). The fusion rate was 87.5% (28/32). Changes in disc height, degree of listhesis, whole lumbar lordosis, and sacral inclination between the pre- and postoperative periods were significant.

The findings suggest that PLIF with autogenous bone chips for double-level isthmic spondylolisthesis could yield good functional short-term results. It seems to be a viable approach in the treatment of double-level isthmic spondylolisthesis 1).

Case series

Fifty-four patients who were managed surgically for treatment of double-level symptomatic isthmic spondylolisthesis were included in this study. Between May 2004 and September 2012, 29 consecutive patients underwent posterior lumbar interbody fusion (PLIF) with autogenous bone chips (group I) at Foshan Hospital of Traditional Chinese Medicine, Guangdong, China. Between March 2005 and December 2013, 25 consecutive patients underwent PLIF with cage (group II) at Zhujiang Hospital of Southern Medical University, Guangdong, China. The mean follow-up periods were 27.2 and 26.8 months, respectively.

The mean VAS scores of back and leg pain significantly decreased from 7.2 to 2.2 and 5.8 to 2.1 in the group I and from 7.0 to 1.9 and 6.1 to 1.8 in the group II, respectively. In the group I, mean ODI scores improved significantly from 54% to 14.2% and, in the group II, from 60% to 12.6%. In both groups, VAS and ODI scores significantly changed from pre- to postoperatively (p<0.001), but postoperative outcome between groups was statistically not significant. Solid union was observed in 27 of 29 patients (89.6%) in the group I and in 22 of 25 patients (88%) in the group II, without statistically significant differences (p>0.05). In both groups, changes in disc height, degree of listhesis, and whole lumbar lordosis between the pre- and postoperative periods were significant.

Clinical and functional outcomes demonstrate no significant differences between groups in treating back and leg pain of adult patients with double-level isthmic spondylolisthesis 2).

Case reports

2017

To the best of Kim et al. knowledge, there has been no report regarding rheumatoid arthritis associated with spinal neuroarthropathy and combined double-level isthmic spondylolisthesis.

They report a rare case of spinal neuroarthropathy with double-level isthmic spondylolisthesis in a rheumatoid arthritis (RA) patient. A 56-year-old female patient under medical treatment for RA during the last 13 years presented aggravating radiating pain to her right lower extremity and a limping gait developed 4 months ago. The disease activity of RA had remained low for a long time. Serial radiographs during last 8-year follow-up showed progressive dislocation at L4-L5 and L5-S1 with double-level isthmic spondylolisthesis and severe destructive status at the last follow-up. The patient underwent decompression and circumferential fusion with sacropelvic fixation and acceptable reduction was obtained.

A RA patient with double-level isthmic spondylolisthesis showed a progressive destructive lesion. In addition to clinical presentations, the imaging findings were very similar to ones of spinal neuroarthropathy. The authors conclude that this Grand Round case probably had SNA secondary to RA and that this, combined with two-level isthmic spondylolisthesis, resulted in her rapidly progressing destructive lumbar lesion 3).

2014

Song et al. present an unusual case of double-level isthmic spondylolisthesis of the lumbar spine. The patient had low-back pain for 20 years and did not respond to conservative treatment. Radiographs revealed bilateral pars defects at L-4 and L-5. Grade 2 isthmic spondylolisthesis was present, both at L4-5 and at L5-S1. The patient underwent decompression, reduction, and posterior lumbar interbody fusion with autogenous bone chips from posterior decompression. At follow-up after 12 months, the patient was free of pain, slippage was corrected, and fusion was achieved. Posterior lumbar interbody fusion with posterior instrumentation and reduction may yield good functional short-term results for double-level spondylolisthesis 4).

2012

An unusual case of a double-level isthmic spondylolisthesis of the lumbar spine in a 38-year-old female was described. The patient had been suffering from low back pain for 8 years and did not respond to conservative treatment. Her medical examination revealed that grade II isthmic spondylolisthesis was present both at L-4 to L-5 and at L-5 to S-1. The patient was managed by surgical treatment. After the reduction of lysthesis with posterior instrumentation, posterior lumbar interbody fusion (PLIF) technique was performed for double level. At a recent follow-up, 1 year after the surgery, the symptoms of the patient were completely resolved, reduction was preserved, and fusion was achieved. PLIF with posterior instrumentation and reduction seems to be a convenient treatment option in the treatment for double-level spondylolisthesis 5).

1)

Song D, Song D, Zhang K, Chen Z, Wang F, Xuan T. Double-level isthmic spondylolisthesis treated with posterior lumbar interbody fusion: A review of 32 cases. Clin Neurol Neurosurg. 2017 Aug 19;161:35-40. doi: 10.1016/j.clineuro.2017.08.007. [Epub ahead of print] PubMed PMID: 28843115.
2)

Song D, Chen Z, Song D, Li Z. Comparison of posterior lumbar interbody fusion (PLIF) with autogenous bone chips and PLIF with cage for treatment of double-level isthmic spondylolisthesis. Clin Neurol Neurosurg. 2015 Nov;138:111-6. doi: 10.1016/j.clineuro.2015.08.012. Epub 2015 Aug 20. PubMed PMID: 26318362.
3)

Kim SI, Kim YH, Lee JW, Kang WW, Ha KY. Rheumatoid arthritis-associated spinal neuroarthropathy with double-level isthmic spondylolisthesis. Eur Spine J. 2017 Jul 28. doi: 10.1007/s00586-017-5220-6. [Epub ahead of print] PubMed PMID: 28755075.
4)

Song D, Chen Z, Song D. Surgical treatment of double-level isthmic spondylolisthesis. J Neurosurg Spine. 2014 Apr;20(4):396-9. doi: 10.3171/2013.12.SPINE13521. Epub 2014 Jan 31. PubMed PMID: 24484307.
5)

Uysal M, Circi E, Ozalay M, Derincek A, Cinar M. The surgical treatment for a rare case of double-level isthmic spondylolisthesis in L4 and L5 lumbar spine: decompression, reduction and fusion. Eur J Orthop Surg Traumatol. 2012 Nov;22 Suppl 1:21-4. doi: 10.1007/s00590-012-0993-0. Epub 2012 Apr 19. PubMed PMID: 26662742.

Update: Multinodular and vacuolating neuronal tumor of the cerebrum

Multinodular and vacuolating neuronal tumor of the cerebrum

Multinodular and vacuolating neuronal tumors of the cerebrum (MVNT) are superficial neuronal tumors in adults that were first documented in 2013 1)

It is a new pattern of neuronal tumour included in the World Health Organization Classification of Tumors of the Central Nervous System 2016, as a unique cytoarchitectural pattern of gangliocytoma.

There are fifteen reports in the literature to date. They are typically associated with late onset epilepsy.

Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation 2).

Differential diagnosis

Dysembryoplastic neuroepithelial tumor – DNET can appear similar but usually is mostly cortical (rather than subcortical) often has bright FLAIR rim focal cortical dysplasia (Type II) high T2 signal deep to cortex is in the same location but is usually associated with a radial glial band (transmantle sign) and with thickened abnormal overlying cortex perivascular spaces location can be similar usually more elongated along vessel long axis fully attenuating on FLAIR 3).

Treatment

MVNTs appear to be benign tumours with very indolent biological behaviour which can, if asymptomatic, be followed with imaging alone. In symptomatic patients (epileptic) surgical resection often controls seizures, with no tumour regrowth reported 4) 5) 6) 7).

Case series

2017

Thom et al. present a series of ten cases and compare their pathological and genetic features to better characterised epilepsy associated malformations including focal cortical dysplasia type II (FCDII) and low-grade epilepsy associated tumours (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi-gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre-operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation 8).


Nunes et al. report 33 cases of presumed multinodular and vacuolating neuronal tumor of the cerebrum that exhibit a remarkably similar pattern of imaging findings consisting of a subcortical cluster of nodular lesions located on the inner surface of an otherwise normal-appearing cortex, principally within the deep cortical ribbon and superficial subcortical white matter, which is hyperintense on FLAIR. Only 4 of the cases are biopsy-proven because most were asymptomatic and incidentally discovered. The remaining were followed for a minimum of 24 months (mean, 3 years) without interval change. They demonstrate that these are benign, nonaggressive lesions that do not require biopsy in asymptomatic patients and behave more like a malformative process than a true neoplasm 9).

2013

Huse et al. report 10 cases of a non-neurocytic, purely neuronal tumor affecting adults. Situated in the cerebral hemispheres, with 7 of 10 confined to the temporal lobes, most presented with seizures as their principal clinical manifestations. On magnetic resosnance imaging (MRI), the tumors generally appeared solid and non-contrast enhancing with minimal diffuse infiltration, edema, or mass effect. Six examples demonstrated internal nodularity. Microscopically, the tumor cells were largely distributed into discrete and coalescent nodules exhibiting varying degrees of matrix vacuolization, principally within the deep cortical ribbon and superficial subcortical white matter. Populating elements ranged from morphologically ambiguous to recognizably neuronal, with only two cases manifesting overt ganglion cell cytology. In all cases, tumor cells exhibited widespread nuclear immunolabeling for the HuC/HuD neuronal antigens, although expression of other neuronal markers, including synaptophysin, neurofilament and chromogranin was variable to absent. Tumor cells also failed to express GFAP, p53, IDH1 R132H, or CD34, although CD34-labeling ramified neural elements were present in the adjoining cortex of seven cases. Molecular analysis in a subset of cases failed to reveal DNA copy number abnormalities or BRAF V600E mutation. Follow-up data indicate that this unusual neuronal lesion behaves in benign, World Health Organization (WHO) grade I fashion and is amenable to surgical control 10).

Case reports

2015

Fukushima et al. report a case of MNVT involving a 37-year-old man who presented with an epileptogenic, superficial solid lesion in the left parietal lobe. Histomorphology of the resected specimen was characterized by nodular lesions with vacuolation. Nodules comprised irregular proliferation of neuronal cells, which ranged from ganglion-like forms to those with indistinct lineage. Immunohistochemical analysis showed that the lesional cells stained positively for HuC/HuD, synaptophysin, and Olig2, and negatively for NeuN, neurofilament, chromogranin A, GFAP, CD34, IDH1(R132H), and BRAF(V600E). Eighteen months following surgery, the patient is well and without neurological deficits. MVNTs are distinctive tumors that should be differentiated from ganglion cell tumors, dysembryoplastic neuroepithelial tumors, and malformation of cortical development 11).

2014

Bodi et al. report the findings in two cases with similar features, a surgical resection and the other an autopsy specimen.Case 1, a 34-year-old female, underwent surgical resection for a multinodular non-enhancing frontal white matter lesion causing intractable epilepsy. Case 2, presented with motor neurone disease (MND) at the age of 71 and MRI scanning revealed extensive multinodular non-enhancing white matter lesions in the temporal lobe. There was no history of epilepsy and post mortem histology confirmed MND.Macroscopically multiple small grey well-formed, discrete and coalescent nodules were seen in the deep cortex and subcortical white matter. On histology, mature-looking neurons with large cytoplasmic vacuoles were distributed in a fibrillary background, where vacuoles were also noted. In the resected tumour scattered oligodendroglia-like cells were present. No ganglion cells were seen. The vacuolated cells exhibited immunopositivity for synaptophysin, HuC/HuD and p62 but were negative for NeuN, neurofilament, GFAP, IDH1, nestin and CD34. Electron microscopy showed non-membrane bound cytoplasmic vacuoles in the neurons and in some neuronal processes. The seizures recurred in Case 1.Some clinicopathological features of this lesion suggest a possible relationship with dysembryoplastic neuroepithelial tumour (DNT) although the morphological features are not typical of DNT. Case 2 demonstrates that MVNT may remain asymptomatic 12).

References

1) , 6) , 10)

Huse JT, Edgar M, Halliday J, Mikolaenko I, Lavi E, Rosenblum MK. Multinodular and vacuolating neuronal tumors of the cerebrum: 10 cases of a distinctive seizure-associated lesion. Brain Pathol. 2013 Sep;23(5):515-24. doi: 10.1111/bpa.12035. Epub 2013 Feb 1. PubMed PMID: 23324039.
2) , 8)

Thom M, Liu J, Bongaarts A, Reinten RJ, Paradiso B, Jäger HR, Reeves C, Somani A, An S, Marsdon D, McEvoy A, Miserocchi A, Thorne L, Newman F, Bucur S, Honavar M, Jacques T, Aronica E. MULTINODULAR AND VACUOLATING NEURONAL TUMOURS IN EPILEPSY: DYSPLASIA OR NEOPLASIA? Brain Pathol. 2017 Aug 19. doi: 10.1111/bpa.12555. [Epub ahead of print] PubMed PMID: 28833756.
4) , 12)

Bodi I, Curran O, Selway R, Elwes R, Burrone J, Laxton R, Al-Sarraj S, Honavar M. Two cases of multinodular and vacuolating neuronal tumour. Acta Neuropathol Commun. 2014 Jan 20;2:7. doi: 10.1186/2051-5960-2-7. PubMed PMID: 24444358; PubMed Central PMCID: PMC3899932.
5) , 11)

Fukushima S, Yoshida A, Narita Y, Arita H, Ohno M, Miyakita Y, Ichimura K, Shibui S. Multinodular and vacuolating neuronal tumor of the cerebrum. Brain Tumor Pathol. 2015 Apr;32(2):131-6. doi: 10.1007/s10014-014-0198-9. Epub 2014 Aug 22. PubMed PMID: 25146549.
7) , 9)

Nunes RH, Hsu CC, da Rocha AJ, do Amaral LLF, Godoy LFS, Watkins TW, Marussi VH, Warmuth-Metz M, Alves HC, Goncalves FG, Kleinschmidt-DeMasters BK, Osborn AG. Multinodular and Vacuolating Neuronal Tumor of the Cerebrum: A New “Leave Me Alone” Lesion with a Characteristic Imaging Pattern. AJNR Am J Neuroradiol. 2017 Jul 13. doi: 10.3174/ajnr.A5281. [Epub ahead of print] PubMed PMID: 28705817.

Update: Cystic metastases

Cystic metastases

Epidemiology

The development of cystic brain metastases remains a relatively rare occurrence.

Etiology

Metastatic brain tumors are normally composed of cystic components, however, the reasons for the cyst formation have not been clearly investigated 1). Stem 2) reported that the brain cyst fluid protein always presents in the inflammatory exudates. Cumings 3) also reported that the cyst fluid formation may be correlated with the tumor degeneration. Gardner et al 4) found that fluid accumulating in brain tumors runs in the normal drainage route, since there are no lymphatic vessels in the tumors.

Gamma knife radiosurgery (GKRS) is occasionally a useful tool for maintaining good brain status in patients with brain metastases (METs). Conversely, Ishikawa et al. experienced patients with delayed cyst formation (DCF) several years after GKRS, a complication not previously reported 5).

Differential diagnosis

The main challenge in discrimination between intracranial cystic lesions is to differentiate benign inflammatory cystic lesions (as cerebral abscess) from malignant cystic lesions (as cystic metastases and cystic glioma) which have totally different management.

Cerebral abscess.

Hydatid cyst.

Other intra-axial cysts, e.g. intracranial arachnoid cyst, neuroglial cyst, porencephalic cyst.

The most common tumors are, hemangioblastoma, pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, tanycytic ependymoma, intraparenchymal schwannoma, desmoplastic infantile ganglioglioma.

Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma 6).

Treatment

In a review, Kim et al. describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. 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 decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes 7).

Case series

2017

Between December 2007 and February 2015, 38 consecutive patients with 40 cystic metastases underwent Ommaya reservoir implantation at our institution. The patient characteristics, treatment parameters, and all available clinical and neuroimaging follow-ups were analyzed retrospectively.

The rate of volume reduction was significantly related to the location of the tube tip inside the cyst. By placing the tip at or near the center, 58.7% reduction was achieved, whereas reduction of 42.6% and 7.7% occurred with deep and shallow tip placement, respectively (p=0.011). Although there was no additional surgery in the center placement group, additional surgeries were performed in 5 out of the 23 deep and shallow cases due to inadequate volume reduction. No other factors were correlated with successful volume reduction.

For adequate volume reduction using the Ommaya reservoir in the treatment of cystic brain metastases prior to stereotactic radiosurgery, the tip of the reservoir tube should be placed at the center of the cyst 8).

2016

Lee et al. retrospectively reviewed the clinical, radiological, and dosimetry data of 37 cystic brain metastases of 28 patients who were treated with GKRS. Cyst drainage was performed in 8 large lesions before GKRS to decrease the target volume. The mean target volume was 4.8 (range, 0.3-15.8) cc at the time of GKRS, and the mean prescription dose was 16.6 (range, 13-22) Gy.

The actuarial median survival time was 17.7 ± 10.2 months, and the primary tumor status was a significant prognostic factor for survival. The actuarial local tumor control rate at 6 and 12 months was 93.1 and 82.3%, respectively. Among the various factors, only prescription dose (>15 Gy) was a significant factor related to local tumor control after multivariate analysis (p = 0.049). Cyst volume or cyst/total tumor volume ratio did not influence local control after GKRS, when the target volume was reduced to about 15 cc after cyst drainage.

According to this results, they suggest that stereotactic radiosurgery should be considered as one of the treatment options for cystic brain metastases, when large tumor volume can be reduced by surgical drainage before radiosurgery, especially for patients with a controlled primary tumor 9).


A study involved 48 patients who were diagnosed with cystic metastatic brain tumors between January 2008 and December 2012 in the Department of Neurosurgery of Nanfang Hospital Southern Medical University (Guangzhou, China). Every patient underwent Leksell stereotactic frame, 1.5T magnetic resonance imaging (MRI)-guided stereotactic cyst aspiration and Leksell GKRS. Subsequent to the therapy, MRI was performed every 3 months. The results indicated that 48 cases were followed up for 24-72 months, with a mean follow-up duration of 36.2 months. Following treatment, 44 patients (91.7%) exhibited tumor control and 4 patients (8.3%) experienced progression of the local tumor. During this period, 35 patients (72.9%) succumbed, but only 2 (4.2%) of these succumbed to the brain metastases. The total local control rate was 91.7% and the median overall survival time of all patients was 19.5 months. The 1-year overall survival rate was 70.8% and the 2-year overall survival rate was 26.2%. In conclusion, these results indicated that the method of stereotactic cyst aspiration combined with GKRS was safe and effective for patients with large cystic brain metastases. This method is effective for patients whose condition is too weak for general anesthesia and in whom the tumors are positioned at eloquent areas. This method enables patients to avoid a craniotomy, and provides a good tumor control rate, survival time and quality of life 10).

2014

Between February 2005 and March 2012, a total of 24 patients underwent GKR after cyst aspiration for 29 cystic metastatic brain tumors. The median age was 60 years (range, 18-81). The number of male patients was 18 and that of female patients 6. Most of the patients were in class II (87.5%) based on the data of the Radiation Therapy Oncology Group using recursive partitioning analysis. We analyzed the changes in tumor volume, the local control rate, intracranial progression-free survival (PFS) and overall survival (OS).

Before aspiration, the mean total tumor volume was 32.7 cm(3) (range, 12.1-103.3) and cystic volume was 18.6 cm(3) (range, 8-72.3). The mean duration of cyst drainage was 1 day (range, 1-2). The mean amount of aspiration was 16.8 cm(3) (range, 6-67.4). After aspiration, the total mean volume was 12.4 cm(3) (range, 3.7-38.1) and cystic volume was 2.0 cm(3) (range, 0.1-9.5). The nature of the cyst was serous in 18, serous and hemorrhagic in 3, and serous and necrotic in 8. The median prescription dose was 16 Gy (range, 14-20). There was no treatment-related complication. The local control rate was 58.6% (17/29). The median survival to local recurrence was 6.0 (±1.42) months. During the follow-up period, an Ommaya reservoir was placed in 3 patients. Insertion of an Ommaya reservoir and whole-brain radiotherapy (WBRT) or GKR were done in 2 patients, WBRT in 2, GKR in 1 and operation in 1. The median intracranial PFS and OS after intracranial metastasis was 5.2 (±0.42) and 6.8 (±0.38) months.

Cyst aspiration and GKR were feasible and safe but not very efficient, which could be an alternative option for large cystic metastases in patients who could not expect longer survival time 11).

2013

Ebinu et al. reviewed a prospectively maintained database of brain metastases patients treated between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response.

A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component.

This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates 12).

2012

Between 2005 and 2010, 25 cystic metastases in 25 patients were treated at Dokkyo Medical University. The patients first underwent MRI and stereotactic aspiration of the cyst while stationary in a Leksell stereotactic frame; immediately afterward, the patients underwent a second MR imaging session and Gamma Knife treatment. Tumor volume reduction, tumor control rate, and overall survival were examined.

Tumor volume, including the cystic component, decreased from 8.0-64.2 cm(3) (mean 20.3 cm(3)) to 3.0-36.2 cm(3) (mean 10.3 cm(3)) following aspiration, and the volume of 24 of 25 lesions decreased to less than 16.6 cm(3), which is equivalent to the volume of a 3.16-cm sphere. At least 20 Gy was delivered to the entire lesion in 24 of 25 cases. Good tumor control was obtained in 16 of 21 cases that could be evaluated during a median follow-up period of 11 months (range 1-27 months); however, reaccumulation of cyst contents was observed in 2 patients who required Ommaya reservoir placement.

The 1-day aspiration plus GKS procedure is an effective and time-efficient treatment for large cystic brain metastases 13).

2009

Hydrofiber dressing is a sodium carboxymethylcellulose hydrocolloid polymer with high fluid-absorptive capacity. This material was originally used as a dressing for exudative wounds. Hydrofiber dressing was used for 8 patients with cystic-type metastatic brain tumor. Tumor removal was performed after hydrofiber dressing was inserted into the cyst cavity to transform the tumor into a solid-type tumor.

Transformation of cystic-type metastatic brain tumors into smaller solid-type tumors using hydrofiber dressing facilitated en bloc resection of tumor. The dressing also absorbed residual cyst fluid and was thus also effective in preventing intraoperative dissemination of tumor cells. This approach enabled ideal en bloc resection in all patients. There were no adverse events.

These findings suggest hydrofiber dressing may be useful in surgery for cystic-type metastatic brain tumors 14).

2008

Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 +/- 11 years, range 38-75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score >or= 70; and 5) histological diagnosis of a malignant tumor.

Non-small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8-68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2-32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12-25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3-64.1%) and 34.2% (95% confidence interval 23.1-45.3%). Local tumor control was achieved in 91.3% of the patients.

The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis 15).

Case reports

2015

A study describes the first case of histopathologically-confirmed brainstem metastasis originating from lung adenosquamous carcinoma, and discusses the outcomes of treatment by stereotactic aspiration combined with gamma knife radiosurgery (GKRS). A 59-year-old female presented with a cystic mass (15×12×13 mm; volume, 1.3 cm3) located in the pons, two years following surgical treatment for adenosquamous carcinoma of the lung. The patient received initial GKRS for the lesion in the pons with a total dose of 54.0 Gy, however, the volume of the mass subsequently increased to 3.9 cm3 over a period of three months. Computed tomography-guided stereotactic biopsy and aspiration of the intratumoral cyst were performed, yielding 2.0 cm3 of yellow-white fluid. Histology confirmed the diagnosis of adenosquamous carcinoma. Aspiration provided immediate symptomatic relief, and was followed one week later by repeat GKRS with a dose of 12.0 Gy. The patient survived for 12 months following the repeat GKRS; however, later succumbed to the disease after lapsing into a two-week coma. The findings of this case suggest that stereotactic aspiration of cysts may improve the effects of GKRS for the treatment of cystic brainstem metastasis; the decrease in tumor volume allowed a higher radiation dose to be administered with a lower risk of radiation-induced side effects. Therefore, stereotactic aspiration combined with GKRS may be an effective treatment for brainstem metastasis originating from adenosquamous carcinoma 16).

2009

A 71-year-old man who was admitted to the emergency department after an episode of loss of consciousness. On neurological examination a left hemiparesis was observed. The patient’s previous history entailed a total cystectomy and radical prostatectomy 7 months ago because of a transitional cell carcinoma (TCC) of the urinary bladder. Brain imaging work-up revealed a cystic lesion with perifocal edema in the right frontal lobe. The patient was operated and the histological diagnosis was consistent with a metastatic carcinoma, with morphological, histochemical and immunohistochemical features comparable to those of the primary tumor. Postoperative the patient was in excellent neurological state and received complementary chemotherapy and total brain irradiation. Additional imaging and laboratory examinations excluded other metastatic lesion. The patient died 18 months later due to systemic disease. Although intracranial metastases from TCC of urinary bladder have a low incidence, in follow-up examinations any alterations in neurological status in these patients should be thoroughly evaluated 17).


Cystic brain metastases from small-cell lung carcinomas are exceedingly rare and neurosurgical operations are not suitable for those cases considering invisible micrometastases. A 34-year-old female patient presented with small-cell lung carcinoma that metastasized to the brain as a solitary cyst with a thin wall 24 months after a good partial response to initial chemoradiotherapy. The brain mass volume and the main symptom of left hemiplegia, which made the Karnofsky performance status (KPS) fall to 30%, did not respond to whole brain irradiation. Therefore, an Ommaya reservoir was inserted, which dramatically improved the KPS to 70%. This minimally invasive surgical strategy is suitable even for patients with a poorer KPS bearing cystic brain metastases 18).

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