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In the multimodality treatment of complex brain arteriovenous malformations (AVMs), the role of endovascular embolization is not fully elucidated. To assess the risk of embolization, we retrospectively evaluated the outcomes of endovascular treatment for AVM, focusing on the embolization-related complications.The present study included patients with brain AVM who underwent embolization at our hospital between April 2011 and May 2021. Risk factors for peri- and postoperative complications were analyzed.During the study period, 36 AVMs were treated during 58 embolization sessions. The goal of the embolization was preoperative in 24 (67%), pre-radiosurgical in 9 (25%), and palliative in 3 (8%) cases. The overall complication rate was 43% (25 of 58) per session and 36% (13 of 36) per patient. Ischemic and hemorrhagic complications were observed in 14 (24%) and 14 (24%) cases, respectively. n-Butyl cyanoacrylate (n-BCA) embolization was detected as the significant risk for postoperative hemorrhage in the univariate (79% vs. 36%, P = 0.012; Fisher exact test) and the multivariable analysis (odds ratio 4.90, 95% confidence interval 1.08-22.2, P = 0.039). The number of embolized feeder in a single session also tended to be higher in a hemorrhagic complication group (median 3.5 vs. 2.0, P = 0.11; Mann-Whitney U-test).The risk of embolization in multimodality treatment for complex brain AVM was substantial. n-BCA embolization may carry a higher risk of postoperative hemorrhage. An accumulation of cases is awaited to investigate the effectiveness of minimal target embolization in the future.

Cerebrovascular malformations comprise abnormal development of cerebral vasculature. They can result in hemorrhagic stroke due to rupture of lesions as well as seizures and neurological defects. The most common forms of cerebrovascular malformations are brain arteriovenous malformations (bAVMs) and cerebral cavernous malformations (CCMs). They occur in both sporadic and inherited forms. Rapidly evolving molecular genetic methodologies have helped to identify causative or associated genes involved in genesis of bAVMs and CCMs. In this review, we highlight the current knowledge regarding the genetic basis of these malformations.

This study aimed to assess the risk factors for the recurrence of WHO grade I intracranial meningiomas using the Brain Tumor Registry of Japan (BTRJ) database. We extracted the data of 4641 patients with intracranial WHO grade I meningiomas treated only by surgical resection between 2001 and 2008. We conducted complete data analysis (n = 3690) and multiple imputation analysis (n = 4641) to adjust for missing data on tumor size. The influence of factors including age, sex, size, extent of resection, location, and preoperative symptoms on PFS was assessed. Univariate analyses of the complete data set showed that age did not affect PFS; however, male sex (p 0.001), tumor size ≥ 30 mm (p 0.001), low extent of resection, tumor location at the skull base (p 0.001), and the presence of preoperative symptoms (p 0.001) were risk factors for a significantly shorter PFS. Multivariate analysis demonstrated that male sex (p 0.001) and presence of preoperative symptoms (p = 0.027) were independent risk factors for shorter PFS alongside large tumor size (p 0.001) and non-gross total resection (p 0.001). These results were confirmed for the imputed dataset. While most previous large nationwide studies of meningiomas have evaluated overall survival, progression-free survival has yet to be thoroughly examined. This study suggests that even histologically benign meningiomas may have a sex difference in postoperative behavior. This observation may provide clues to understanding the mechanism of meningioma cell proliferation.

OBJECTIVE The major concern about ruptured arteriovenous malformations (rAVMs) is recurrent hemorrhage, which tends to preclude stereotactic radiosurgery (SRS) as a therapeutic modality for these brain malformations. In this study, the authors aimed to clarify the role of SRS for rAVM as a stand-alone modality and an adjunct for a remnant nidus after surgery or embolization. METHODS Data on 410 consecutive patients with rAVMs treated with SRS were analyzed. The patients were classified into groups, according to prior interventions: SRS-alone, surgery and SRS (Surg-SRS), and embolization and SRS (Embol-SRS) groups. The outcomes of the SRS-alone group were analyzed in comparison with those of the other two groups. RESULTS The obliteration rate was higher in the Surg-SRS group than in the SRS-alone group (5-year cumulative rate 97% vs 79%, p < 0.001), whereas no significant difference was observed between the Embol-SRS and SRS-alone groups. Prior resection (HR 1.78, 95% CI 1.30–2.43, p < 0.001), a maximum AVM diameter ≤ 20 mm (HR 1.81, 95% CI 1.43–2.30, p < 0.001), and a prescription dose ≥ 20 Gy (HR 2.04, 95% CI 1.28–3.27, p = 0.003) were associated with a better obliteration rate, as demonstrated by multivariate Cox proportional hazards analyses. In the SRS-alone group, the annual post-SRS hemorrhage rates were 1.5% within 5 years and 0.2% thereafter and the 10-year significant neurological event–free rate was 95%; no intergroup difference was observed in either outcome. The exclusive performance of SRS (SRS alone) was not a risk for post-SRS hemorrhage or for significant neurological events based on multivariate analyses. These results were also confirmed with propensity score–matched analyses. CONCLUSIONS The treatment strategy for rAVMs should be tailored with due consideration of multiple factors associated with the patients. Stand-alone SRS is effective for hemorrhagic AVMs, and the risk of post-SRS hemorrhage was low. SRS can also be favorably used for residual AVMs after initial interventions, especially after failed resection.

BACKGROUND The precise etiology of dural arteriovenous fistula (DAVF) is still unknown. The authors reported a case of delayed postoperative sigmoid sinus (SS) DAVF secondary to SS thrombosis after resection of a foramen magnum meningioma through a suboccipital craniotomy. OBSERVATIONS The authors visualized the clear architecture of the DAVF using fusion three-dimensional computer graphics (3DCG) images reconstructed from multimodal imaging studies. These fusion 3DCG images revealed that the feeders of the DAVF had connected through neovascularization to the SS at the previous thrombus site. The authors also reviewed previously reported cases of DAVFs that developed after craniotomy. LESSONS This study indicated that SS stenosis and occlusion with sinus thrombosis are possible risk factors for delayed postoperative DAVF that demand special consideration.

Objective To examine a potential association between intranidal microhemodynamics and rupture using a phase-contrast magnetic resonance angiography (PCMRA)-based flow quantification technique in arteriovenous malformations (AVMs). Methods We retrospectively collected data on 30 consecutive patients with AVMs (23 unruptured and 7 ruptured). Based on PCMRA data, maximal (Vmax) and mean (Vmean) intranidal velocities were calculated. Logistic regression analysis was performed to assess factors associated with previous AVM rupture. Results All ruptures occurred within 6 months before PCMRA. The mean nidus volume was 4.7 mL. Eleven patients (37%) had deep draining vein(s), and 6 patients (20%) had a deep-seated nidus. The mean ± standard deviation Vmean and Vmax were 9.6 ± 2.8 cm/second and 66.7 ± 26.2 cm/second, respectively. The logistic regression analyses revealed that higher Vmax (P = 0.075, unit odds ratio [OR] = 1.05, 95% confidence interval [95% CI] = 1.00–1.10) was significantly associated with prior hemorrhage. The receiver-operating curve analyses demonstrated that a Vmean of 10.8 cm/second (area under the curve = 0.671) and Vmax of 90.2 cm/second (area under the curve = 0.764) maximized the Youden Index. A Vmax > 90 cm/second was significantly associated with AVM rupture both in the univariate (P = 0.025, OR = 9.0, 95% CI = 1.3–61.1) and multivariate (P = 0.008, OR = 51.7, 95% CI = 2.8–968.3) analyses. Conclusions Presence of faster velocities in intranidal vessels may suggest aberrant microhemodynamics and thus be associated with AVM rupture. PCMRA-based velocimetry seems to be a promising tool to predict future AVM rupture.

This study aimed to improve the understanding of the role of adjuvant radiotherapy (AR) after subtotal resection (STR) of World Health Organization (WHO) grade I meningiomas. We retrospectively reviewed the Brain Tumor Registry of Japan database. Among 7341 patients diagnosed with intracranial meningioma during 2001–2008, we identified 406 patients with WHO grade I meningioma treated with STR as initial treatment. Data on progression-free survival (PFS) were assessed for their relevance to clinical factors including age, sex, tumor location and size, presence of preoperative symptoms, and AR. AR was administered for 73 patients (18.0%). Regrowth occurred in 90 cases (22.2%) during the median follow-up period of 6.0 years (interquartile range, 2.7–7.7 years). Multivariate Cox regression analysis of the entire cohort showed that no AR was associated with significantly shorter PFS (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.33–5.42, p = 0.004). The therapeutic effect of AR was confirmed for skull base, but not non-skull base, meningiomas (p = 0.003 and 0.69, respectively). Propensity score matching analysis balanced the influence of confounding factors to generate AR+ and AR− cohorts of 73 patients each. PFS was significantly longer in the AR+ cohort than in the AR− cohort (HR 3.46, 95% CI 1.53–8.59, p = 0.003). Subgroup analysis demonstrated the favorable effect of AR only for skull base meningiomas. Our study revealed that AR improves tumor control after STR in WHO grade I meningiomas. However, this beneficial effect might be limited to skull base meningiomas.

Orbital cavernous venous malformation (OCVM) is a sporadic vascular anomaly of uncertain etiology characterized by abnormally dilated vascular channels. Here, we identify a somatic missense mutation, c.121G > T (p.Gly41Cys) in GJA4, which encodes a transmembrane protein that is a component of gap junctions and hemichannels in the vascular system, in OCVM tissues from 25/26 (96.2%) individuals with OCVM. GJA4 expression was detected in OCVM tissue including endothelial cells and the stroma, through immunohistochemistry. Within OCVM tissue, the mutation allele frequency was higher in endothelial cell-enriched fractions obtained using magnetic-activated cell sorting. Whole-cell voltage clamp analysis in Xenopus oocytes revealed that GJA4 c.121G > T (p.Gly41Cys) is a gain-of-function mutation that leads to the formation of a hyperactive hemichannel. Overexpression of the mutant protein in human umbilical vein endothelial cells led to a loss of cellular integrity, which was rescued by carbenoxolone, a non-specific gap junction/hemichannel inhibitor. Our data suggest that GJA4 c.121G > T (p.Gly41Cys) is a potential driver gene mutation for OCVM. We propose that hyperactive hemichannel plays a role in the development of this vascular phenotype.

Background Understanding the complex anatomy of neurostructures is very important in various stages of medical education, from medical students to experienced neurosurgeons, and, ultimately, for the knowledge of human beings. Objective To develop an interactive computer graphics (CG) anatomic head model and present the current progress. Methods Based on the prior head 3-dimensional CG (3DCG) polygon model, 23 additional published papers and textbooks were consulted, and 2 neurosurgeons and 1 CG technician performed revision and additional polygon modeling. Three independent neurosurgeons scored the clear visibility of anatomic structures relevant to neurosurgical procedures (anterior petrosal and supracerebellar infratentorial approaches) in the integrated 3DCG model (i model) and patients' radiological images (PRIs) such as those obtained from computed tomography, magnetic resonance imaging, and angiography. Results The i model consisted of 1155 parts (.stl format), with a total of 313 763 375 polygons, including 10 times more information than the foundation model. The i model was able to illustrate complex and minute neuroanatomic structures that PRIs could not as well as extracranial structures such as paranasal sinuses. Our subjective analysis showed that the i model had better clear visibility scores than PRIs, particularly in minute nerves, vasculatures, and dural structures. Conclusion The i model more clearly illustrates minute anatomic structures than PRIs and uniquely illustrates nuclei and fibers that radiological images do not. The i model complements cadaveric dissection by increasing accessibility according to spatial, financial, ethical, and social aspects and can contribute to future medical education.

The facial colliculus (FC), an important landmark for planning a surgical approach to brainstem cavernous malformation (BCM), is a microstructure; therefore, it may be difficult to identify on magnetic resonance imaging (MRI). Three-dimensional (3D) images may improve the FC-identification certainty; hence, this study attempted to validate the FC-identification certainty between two-dimensional (2D) and 3D images of patients with a normal brainstem and those with BCM. In this retrospective study, we included 10 patients with a normal brainstem and 10 patients who underwent surgery for BCM. The region of the FC in 2D and 3D images was independently identified by three neurosurgeons, three times in each case, using the method for continuously distributed test results (0–100). The intra- and inter-rater reliability of the identification certainty were confirmed using the intraclass correlation coefficient (ICC). The FC-identification certainty for 2D and 3D images was compared using the Wilcoxon signed-rank test. The ICC (1,3) and ICC (3,3) in both groups ranged from 0.88 to 0.99; therefore, the intra- and inter-rater reliability were good. In both groups, the FC- identification certainty was significantly higher for 3D images than for 2D images (normal brainstem group; 82.4 vs. 61.5, P = .0020, BCM group; 40.2 vs. 24.6, P = .0059 for the unaffected side, 29.3 vs. 17.3, P = .0020 for the affected side). In the normal brainstem and BCM groups, 3D images had better FC-identification certainty. 3D images are effective for the identification of the FC.

Purpose: To evaluate a new method that registers phase-contrast magnetic resonance angiography images to time-of-flight magnetic resonance angiography images. Methods: Magnetic resonance angiography datasets of 10 healthy volunteers obtained by using two modalities (phase-contrast magnetic resonance angiography and time-of-flight magnetic resonance angiography) were preprocessed. Specifically, vessel regions were extracted using the region growing method with a threshold of 10% of the signal intensity maximum or 50% of the signal intensity maximum for phase-contrast magnetic resonance angiography images and time-of-flight magnetic resonance angiography images, respectively. Then, the normalized mutual information method was used to determine spatial positions, and registration between non-preprocessed phase-contrast magnetic resonance angiography and time-of-flight magnetic resonance angiography was performed using the spatial position information. Misalignment of 3 anatomical points was used to compare the accuracy of registration in this data group (the proposed method group) to that in the data group without registration (the non-registration group) and that in the data group subjected to normalized mutual information-based registration without preprocessing (the non-preprocessing group). Results: The mean misalignment of 3 anatomical points ± standard error was 1.69 ± 0.11 mm in the proposed method group, and 2.77± 0.13 mm and 90.28 ± 8.24 mm in the non-registration group and non-preprocessing group, respectively. The mean misalignment of 3 anatomical points was significantly smaller in the proposed method group than in the non-registration group (p = 0 001). Conclusions: The proposed preprocessing and registration method improved the accuracy of normalized mutual information-based registration between phase-contrast magnetic resonance angiography images and time-of-flight magnetic resonance angiography images.

Objective Gamma knife radiosurgery (GKRS) is commonly used to treat vestibular schwannomas (VSs). The risk of complications from GKRS decreases at lower doses, but it is unknown if long-term tumor control is negatively affected by dose reduction. Study design This was a retrospective case review and analysis of patient data. Setting Tertiary referral center. Patients Patients with VSs who underwent GKRS between 1990 and 2007 at the authors' institution. Intervention(s) The subjects were divided into two cohorts based on the prescribed doses of radiation received: a 12 Gy cohort (96 patients) with a follow-up period of 124 months and a >12 Gy cohort (118 patients) with a follow-up period of 143 months. Main outcome measures Tumor control rates at 10 to 15 years, frequency of facial and trigeminal nerve complications, and hearing function. Results The 10 to 15-year tumor control rates were 95% in the 12 Gy cohort and 88% in the > 12 Gy cohort, but the differences were not significant. Compared with the >12 Gy cohort, facial and trigeminal nerve deficits occurred significantly less frequently in the 12 Gy cohort, with the 10-year cumulative, permanent deficit-free rates being 2% and 0%, respectively. Multivariate analyses revealed that treatment doses exceeding 12 Gy were associated with a significantly higher risk for cranial nerve deficits. The percentage of subjects retaining pure-tone average ≤ 50 dB at the final follow-up did not significantly differ between the cohorts (12 Gy cohort, 30% and >12 Gy cohort, 33%; p = 0.823). Conclusions Dose reduction to 12 Gy for GKRS to treat VSs decreased facial and trigeminal nerve complications without worsening tumor control rates.

Background Ganglion cysts mostly occur in the knuckles and wrists, but they rarely present in the odontoid process and can cause neurological symptoms by compressing the spinal cord. They are mostly localized in the epidural space, but may very rarely appear in the intradural space. There are no reports of cases of intradural ganglion cyst involving syringobulbia. Case Description We report the presentation and management of 2 cases of an intradural ganglion cyst of the odontoid process. Several treatment options for ganglion cysts of the odontoid process have been reported, such as rest and use of a neck collar, posterior decompression and fusion, and transoral anterior decompression. Because our 2 cases progressed rapidly and had severe neurological symptoms, surgical treatment was performed for rapid decompression and definitive pathological diagnosis. The mass was resected as much as possible using the lateral occipital fossa approach, and the operation was completed without dissection of the brain stem or manipulation of the syringobulbia. Postoperatively, neurological symptoms promptly improved, and the syringobulbia reduced. Conclusions For intradural ganglion cysts with syringobulbia, we suggest relief of the compression by resection of the mass and treatment of the syringobulbia in 2 stages, if necessary, to avoid the risk of damage to the brainstem.

OBJECTIVEThe management of vestibular schwannoma (VS) remains controversial. One commonly cited advantage of microsurgery over other treatment modalities is that tumor removal provides the greatest chance of long-term cure. However, there are very few publications with long-term follow-up to support this assertion. The purpose of the current study is to report the very long-term risk of recurrence among a large historical cohort of patients who underwent microsurgical resection.METHODSThe authors retrospectively reviewed the medical records of patients who had undergone primary microsurgical resection of unilateral VS via a retrosigmoid approach performed by a single neurosurgeon-neurotologist team between January 1980 and December 1999. Complete tumor removal was designated gross-total resection (GTR), and anything less than complete removal was designated subtotal resection (STR). The primary end point was radiological recurrence-free survival. Time-to-event analyses were performed to identify factors associated with recurrence.RESULTSFour hundred fourteen patients met the study inclusion criteria and were analyzed. Overall, 67 patients experienced recurrence at a median of 6.9 years following resection (IQR 3.9–12.1, range 1.2–22.5 years). Estimated recurrence-free survival rates at 5, 10, 15, and 20 years following resection were 93% (95% CI 91–96, 248 patients still at risk), 78% (72–85, 88), 68% (60–77, 47), and 51% (41–64, 22), respectively. The strongest predictor of recurrence was extent of resection, with patients who underwent STR having a nearly 11-fold greater risk of recurrence than the patients treated with GTR (HR 10.55, p < 0.001). Among the 18 patients treated with STR, 15 experienced recurrence at a median of 2.7 years following resection (IQR 1.9–8.9, range 1.2–18.7). Estimated recurrence-free survival rates at 5, 10, 15, and 20 years following GTR were 96% (95% CI 93–98, 241 patients still at risk), 82% (77–89, 86), 73% (65–81, 46), and 56% (45–70, 22), respectively. Estimated recurrence-free survival rates at 5, 10, and 15 years following STR were 47% (95% CI 28–78, 7 patients still at risk), 17% (5–55, 2), and 8% (1–52, 1), respectively.CONCLUSIONSLong-term surveillance is required following microsurgical resection of VS even after GTR. Subtotal resection alone should not be considered a definitive long-term cure. These data emphasize the importance of long-term follow-up when reporting tumor control outcomes for VS.

Background and importance The occipital transtentorial approach is used to address lesions at the posterior incisural space or upper cerebellum. This approach is rarely used, making standardization of the surgical procedure challenging. Here we describe the effectiveness of indocyanine green (ICG) and dye markings before tentorial incision in charting a safe and bloodless surgical trajectory for improved manoeuvrability. Clinical presentation The first case was a 40-year-old man with a residual pineal mass after chemoradiation therapy for pathologically-proven germinoma. Surgical resection was performed via left occipital craniotomy. Incision of the left cerebellar tentorium by a radiofrequency knife was preceded by visualization of the straight sinus and venous lake, which were marked with dye, enabling safe entry into the quadrigeminal cistern. Finally, total-resection of the mature teratoma was achieved. The second case was a 50-year-old man with an enhancing mass at the cerebellar vermis and left hemisphere. Left occipital craniotomy was followed by ICG administration, illuminating the straight sinus and a complex structure of dural venous channels, which were marked with dye. This visualization maximized the tentorial incision by carefully avoiding venous structures and widely exposed the upper cerebellum. Subtotal-resection of the tumor was achieved, with a diagnosis of glioblastoma. Conclusion ICG administration and dye marking are feasible and useful methods for precise identification/visualization of venous structures. They enable maximization as well as safe and appropriate tentorial incision to provide a sufficient surgical corridor for the occipital transtentorial approach.

Background Intracranial arterial dissection (IAD) is known to exhibit various patterns of arterial imaging features such as stenosis and dilation; however, the genetic background of IAD has not been elucidated so far. RNF213 was recently identified as a susceptibility gene for moyamoya disease (MMD) and intracranial artery stenosis (ICAS). More recently, RNF213 p.Arg4810Lys also has been shown to be associated with various systemic vascular diseases. RNF213 p.Arg4810Lys is beginning to attract attention as a genetic factor that causes systemic vascular disease. Case Description Herein, we report a rare case of de novo progression of the intracranial vascular lesion with the RNF213 p.Arg4810Lys variant, which first presented IAD of the middle cerebral artery (MCA) with subarachnoid hemorrhage, second progressed into ICAS, and finally evolved into MMD-like angiogenesis over 6 years. Conclusions This case suggests that IAD of the MCA could be associated with RNF213 p.Arg4810Lys variant. This genetic variant could also have a key role in the overlap among the different disease states. A large-scale genetic analysis study of the IADs of the anterior circulation is needed. To qualify the significance of RNF213 p.Arg4810Lys variant as a stroke risk allele, accumulation of various cases of cerebrovascular lesions would be essential.

Background Reports of cases diagnosed as Moyamoya disease (MMD) after stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) are extremely rare. In recent years, ring finger protein 213 (RNF213) has been identified as a susceptibility gene of MMD, but the mechanism by which MMD develops remains unclear. Those cases of de novo development of MMD may provide some clues to clarify the mechanism of progression of MMD. Case Description We report the case of de novo MMD that developed after SRS for AVM. This patient presented with a variant of the RNF213 gene. The intracranial internal carotid artery was not within the irradiation field; therefore it was obvious that the development of MMD was not caused by the direct effect of radiation in the current case study. Moreover, we demonstrated the decrease in velocity in the internal carotid artery prior to the development of MMD using phase-contrast magnetic resonance angiography. Previous studies demonstrated that progression of the pathological condition in the cerebral arteries in response to hemodynamic changes is enhanced in patients with RNF213 variants. Conclusions Our findings indicate that the changes in the intracranial hemodynamics after SRS for AVM could trigger the de novo onset of MMD in patients with a genetic predisposition for the RNF213 variant.

Background Although the embolization of lenticulostriate artery feeders is often warranted in the treatment of brain arteriovenous malformations, it is technically challenging due to steep and repeated angulations. Here, we describe our novel technique of navigating a flow-guided microcatheter into lenticulostriate artery feeders using the strong support provided by an S-shaped distal access catheter. Methods We reviewed our retrospective cohort of brain arteriovenous malformations, in which lenticulostriate artery feeders were attempted to embolize. Result During the study period, endovascular embolization was performed in 25 arteriovenous malformations cases. Of these, eight lenticulostriate artery feeders were present in six cases (24%). In two cases, lenticulostriate artery feeder catheterization was avoided from the beginning due to the small diameters of the feeders. After all, microcatheter navigation for lenticulostriate artery feeders were attempted in four cases with six lenticulostriate artery feeders. In all the six feeders, the S-shaped distal access catheter was successful in supporting the microcatheter to advance distally to the lenticulostriate artery feeders, even if other approaches were unsuccessful. Of the six catheterized lenticulostriate artery feeders, four were embolized. Symptomatic infarction in the lenticulostriate artery territory and mild vasospasm occurred in two cases each, but they did not result in permanent neurological deficits. Conclusion Although some potential complications need to be considered, the S-shaped distal access catheter technique appears to be an effective alternative approach to gaining access to difficult feeders of arteriovenous malformations.

Background Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)–positive ALCL have been reported so far, with no reported cases of a small cell variant. Case Description A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE). Conclusions In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment.