DOWNLOAD PDF RADIOSURGERY FOR CAVERNOUS MALFORMATIONS IN BASAL GANGLIA, THALAMUS AND BRAINSTEM KIDA, Y

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1 Chapter 1 : Stereotactic radiosurgery for cavernous malformations â Mayo Clinic Most of the lesions were located in the brainstem, followed by the lobar region, cerebellum, thalamus, and basal ganglia [Figure 1]. They were separated into deep (brainstem, basal ganglia, thalamus) and superficial locations (cerebellar and lobar). Dosage at the tumor margin was stratified into 2 groups: The decision to stratify into above or below 13 Gy was retrospectively. Follow-up The posttreatment observation period was the date of the initial GKS procedure. MRI studies and clinical assessment were performed at 6 months intervals until the occurrence of surgical intervention or death from another cause. The last MRI scan for all patients was recorded during the follow-up period. Side effects and any clues of hemorrhage, including new foci, volume expansion of irradiated lesions, and edematous changes after GKS were also observed during the follow-up period. The annual hemorrhage rate pre and postgks was recorded in patient-years based on definitions presented by Lee et al. A total of There were episodes of hemorrhage through this period. Data are given as mean, median, and standard deviation. Ethics In this center, at the beginning of treatment, all patients gave their informed consent to each study protocol. Results The last MRI scan was achieved at median follow-up time All of the cases participated in regularly scheduled follow-up for at least 2 years. Temporary neurological events without radiological evidence of hemorrhage or edema occurred in 3 patients. In seven patients, the symptom got worse with growth of the lesions and increased surrounding edema indicative of radiation effect from 5 to 9 months after GKS 1 headache and focal neurological symptoms in 6. The prescribed marginal dose was ranging from 14 to 17 Gy in these cases. Ninety-nine patients with a single lesion and one with two lesions were treated. Overall, CMs were seen, and 3. Median volume of the lesions was Survival Overall, the neurological status was either stable, transient worsening or improved in In the present study, complications due to radiation developed with marginal dose as low as 13 Gy. Two patients developed hemorrhage after GKS. One patient with rebleeding and acute hydrocephaly underwent ventriculoperitoneal shunt insertion 2 months after GKS. He had been treated with marginal dose of 14 Gy for lesion volume of Six patients died unrelated to the treated CMs. Late-delayed AREs is needed for assessment over longer time periods. Discussion Our findings were promising in treating patients with cavernomas. However, as a guide, it should be noted that gamma-knife for CM should be subject to scrutiny as it is generally not accepted as a treatment modality for these lesions. Some authors have found that there was no difference in the hemorrhage rate before and after GKS. However, at present, there is no way to predict the behavior of CMs for hemorrhage. Previously reported mean rates of the volume reduction after radiosurgery for CMs varied from However, it is unclear whether shrinkage of the bulk is really induced by radiation or other factors and needs to be investigated in the future. The optimal dose of CMs for a positive response and minimum side effects is controversial. The radiation-related complication in our cases confirmed the value of such a treatment strategy. As in a study by Lee et al. The optimal dose and threshold for radiation-related complication for CMs have not been defined up till now. It seems that there is a need to explore the issue further particularly for specific sites such as the brain stem. However, the natural history of benign lesions should be considered for better outcomes. However, we were not able to explain differences in complication rates and future studies are recommended. Finally, although surgical resection is the first option for CMs patients,[ 3 ] GKS is an alternative to conservative therapy in cases at a surgically inaccessible site and is recommended. There are several principle weaknesses in this study. The first is the retrospective nature and the inherent limitations of this methodology. Second, due to a limited number of patients with prior surgery, we cannot compare these outcomes. Third, there were differences in treatment and variation in tumor location for patients prior to entering to the study. Thus, the findings should be interpreted with caution. Conclusion The GKS for cavernomas appears to be a safe and beneficial treatment in carefully selected patients. Footnotes Conflict of Interest: Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated Page 1

2 patients. Handbook of Neurosurgery; pp. Supratentorial and Infratentorial Cavernous Malformations WB Saunders Company; Stereotactic radiosurgery for deep-seated cavernous malformations: A move toward more active, early intervention. The role of Gamma Knife surgery. Histopathological changes in cerebral arteriovenous malformations following Gamma Knife radiosurgery. Progress in Neurological Surgery. Radiosurgery and Pathological Fundamentals; pp. Long-term results after stereotactic radiosurgery for patients with cavernous malformations. Kida Y, Hasegawa T. Radiosurgery for cavernous malformations: Results of long-term follow-up. Stereotactic radiosurgery of angiographically occult vascular malformations: LINAC radiosurgery for intracranial cavernous malformation: Radiosurgery for cavernous malformations. Radiosurgery of intracranial cavernous malformations. Acta Neurochir Wien ; Stereotactic radiosurgery for cavernous malformations. Gamma knife radiosurgery for cavernous haemangiomas. Reduction of hemorrhage risk after stereotactic radiosurgery for cavernous malformations. Gamma knife radiosurgery of the brain stem cavernous angioma. Korean J Cerebrovasc Surg. Radiosurgery in the treatment of brain cavernomas. Experience with 17 lesions treated in 15 patients. Stereotactic radiosurgery for cavernous malformations: Karlsson B, Tsai YT. Radiosurgery for cavernomas â A meta-analysis. Pan Arab J Neurosurg. The natural history of intracranial cavernous malformations. Page 2

3 Chapter 2 : Cavernomas: Outcomes after gamma-knife radiosurgery in Iran Most of the lesions were located in the brainstem, followed by the lobar region, cerebellum, thalamus, and basal ganglia. They were separated into deep (brainstem, basal ganglia, thalamus) and superficial locations (cerebellar and lobar). This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. A group study for symptomatic cavernous malformation CM treated with gamma knife GK surgery was performed. A total of cases collected from 23 GK centers across Japan were included. Hemorrhage was the most common manifestation, followed by seizures and neurological deficits. Most of the lesions were located in the brainstem and basal ganglia, followed by the cerebral or cerebellar hemispheres. The CMs, which had a mean diameter of In terms of hemorrhage-free survival HFS, a marked dissociation was confirmed between the hemorrhage and seizure groups, while no obvious difference was noted between sexes. Superficial CMs located in cerebellum or lobar regions responded to the treatment better than deeply located CMs in the basal ganglia or brainstem. No significant difference of dose-dependent response was seen for three different ranges of marginal dose: Less than 15 Gy, between 15 and 20 Gy, and more than 20 Gy. Complications were more frequent after a marginal dose of over 15 Gy and in patients with lesions more than 15 mm in diameter. The rates of annual hemorrhage were estimated to be 7. The overall hemorrhage rate after radiosurgery was 4. The risk of hemorrhage is considerably reduced after GK treatment. The HFS as well as annual hemorrhage rate after GK treatment was apparently superior to that after conservative treatment for symptomatic CMs. To optimize the success of GK treatment, it is important to reduce the incidence of complications. However, a differential diagnosis from thrombosed arteriovenous malformation AVM, venous anomaly, or capillary hemangioectasia is not always easy. However, most of these lesions are believed to be CMs. A majority of CMs are clinically very silent and are often detected incidentally. Some CM lesions, however, show very aggressive behaviors, with frequent bleeding, intractable seizures, or neurological deficits presenting during a short period of time. Because of this lack of information, the treatment results of surgery or radiosurgery for symptomatic lesions cannot be evaluated precisely. Despite this uncertainty, the aggressive clinical behaviors of s-cms calls for treatment such as surgery or radiosurgery. In this article, the nation-wide results of radiosurgery for s-cms have been summarized and compared with the natural history of s-cms to clarify the role of radiosurgery and microsurgery. With the cooperation of the Scientific Committee of the Japanese Society of Gamma Knife, this multi-institutional retrospective study was planned and conducted with the permission of the Ethics Committee of the participating institutions. In this study, a questionnaire was distributed and the following data were collected from each GK center in Japan. Data on the initial symptoms, location and size of the lesions, and treatment methods used at the time of the first episode were collected. Then, details regarding the radiosurgery procedure including the lesion site, lesion volume, and marginal dose of radiosurgery were investigated. Data on the subsequent occurrence of symptomatic episodes and the treatment used for such episodes as well as the final neurological status and outcome, along with the available imaging studies, were also requested. All the cases treated with GK were symptomatic, chiefly with hemorrhage, and epilepsy, neurological deficits in a few cases. No asymptomatic ones were included in this series. In general, whole lesions including the low-intensity rim were covered for supratentorial and cerebellar CMs, whereas only the core of the lesion was covered for lesions located in the brainstem or basal ganglia. After radiosurgery, follow-up studies using MRI were performed every 3 months during the first year and at least every 6 months thereafter. Hemorrhage was defined as a new area of blood density on CT imaging in association with or without a neurological symptom or sign. New foci of high signal intensity on T1-weighted MR images, volume expansion of the lesions and edematous changes of surrounding brain were also carefully studied. The final clinical status was classified into five categories as follows: Minimal or intermittent nondisabling symptoms; Fair: Moderate disability, independent of others; Poor: Major disability, dependent on Page 3

4 others, progressive symptoms; Dismal: For hemorrhage rates after diagnosis and treatment, survival analysis technique were used to compare Kaplanâ Meier curves with log-rank test. The annual hemorrhage rate AHR was defined as number of hemorrhages divided by total follow-up years. They were treated with GK from to, and with a sufficient follow-up period at least more than 12 months. The patient characteristics, such as their age and sex, the location of the lesion, and the mean lesion size, are listed in [ Table 1 ]. Overall, males and females ranging in age from 7 to 73 years mean age, Most of the lesions were located in the brainstem, followed by the lobar region, cerebellum, thalamus, and basal ganglia [ Figure 1 ]. They were separated into deep brainstem, basal ganglia, thalamus and superficial locations cerebellar and lobar. Page 4

5 Chapter 3 : Management of Cerebral Cavernous Malformations: From Diagnosis to Treatment Gamma knife radiosurgery for intracranial cavernous malformations. Y. KidaRadiosurgery for cavernous malformations in basal ganglia, thalamus and brainstem. Recently, Fleetwood and associates 7 examined the natural history of AVMs in the basal ganglia or thalamus that were managed at Stanford University between and During that year period, 96 patients harboring these lesions were evaluated. With more than total patient-years of conservative management, the annual risk of hemorrhage was 9. Other studies on deeply located AVMs have produced similar findings. According to Lawton and colleagues 18 and Sasaki, et al. Of course, this information has been derived from retrospective studies at academic centers and, therefore, may not truly represent the natural history of this malformation. Nonetheless, these studies demonstrate the significant risk associated with conservative management of AVMs in deep locations. Resection and Endovascular Therapy Making the situation worse is the fact that the treatment options available to patients with AVMs in deep locations are quite limited. Unlike angiographically occult vascular malformations, which can be resected safely by using modern microsurgical techniques, 33, 37 few neurosurgeons commonly recommend resection of deeply located AVMs. Liu and Lee 21 reported 16 cases in which excision of AVMs in the basal ganglia or thalamus was performed before radiosurgery became locally available in Overall, 38 patients underwent 69 embolization sessions before radiosurgery 19 patients, microsurgery five patients, or both radiosurgery and microsurgery 13 patients. Only one patient was treated with endovascular techniques alone. The authors concluded that embolization can obliterate a significant portion of these AVMs and may permit complete obliteration when combined with resection or radiosurgery as part of a multimodal treatment regimen. Radiosurgery of AVMs in Deep Locations As an alternative to resection or endovascular therapy, ra-diosurgery has become the primary treatment option for the majority of patients with deeply located AVMs. The average AVM volume was 1. Three patients experienced bleeding after radiosurgery. One of these patients died and the other two recovered without any deficit. Crocco 4 reported the results of radiosurgery in 33 patients with AVMs located in the basal ganglia region corpus striatum, internal capsule, or thalamus. An average radiation dose of Twenty-six patients participated in at least 6 months of follow-up review and 21 patients in more than 2 years. Crocco concluded that radiosurgical outcomes are similar between patients with AVMs in the basal ganglia region and patients with cortical AVMs and that radiosurgery should be considered the first treatment for patients with AVMs of the basal ganglia region that are smaller than 10 cm3 in volume. Our study provides additional information regarding the results of radiosurgery for patients with deeply located AVMs. First, although the annual rate of postradiosurgical bleeding does not appear to be any different for this group, the neurological risk associated with each hemorrhage appears to be much higher. In this series, five of seven patients died after they experienced hemorrhage from their AVMs. Second, the risk of radiation-related complications was greater for patients with deeply located AVMs than for those with superficially located AVMs. Two factors, dose reduction and exclusion of the nidus from the treated volume, are likely to be the cause of the reduced obliteration rate after radiosurgery of deeply located AVMs. For example, clinical observations and the integrated logistic formula would predict that more than 20 Gy should be a safe margin dose for the AVMs in our series median volume 3. In an attempt to reduce the volume treated, and thus minimize risk of radiation-related complications, it is probable that in the present study the entire nidus was not covered at the time of radiosurgery in more patients than in other studies. Such marginal or geographic misses are the most common cause of failed radiosurgery for AVMs. Less than one half of our patients had an excellent outcome after one or more radiosurgical procedures. Does this mean that radiosurgery is inappropriate for patients with deeply located AVMs? Our results suggest that we can predict those patients who are most likely to be cured of the future risk of hemorrhage with an acceptable level of morbidity. Sixty-seven percent of patients with a radiosurgery-based AV M score of less than 1. In addition, patients with AV M scores between 1. Thus, most patients with AVMs Page 5

6 in deep locations and radiosurgery-based scores below 2. Consequently, radiosurgery may have little impact on outcomes for older patients or for those with large-volume AVMs at deep locations, and observation may be an acceptable treatment strategy for these patients. It remains to be seen whether staged-volume radiosurgery for AVMs can significantly improve the success rate of radiosurgery for patients who are unlikely to be cured after a single session of radiosurgery. Our findings, although sobering, do not take away from the fact that radiosurgery remains the mainstay of care for patients with deeply located AVMs because neither resection nor endovascular therapy provides a better management option for these patients with hard-to-treat lesions. Page 6

7 Chapter 4 : CAVERNOUS MALFORMATIONS OF THE BASAL GANGLIA AND THALAMUS Neurosurger CAVERNOUS MALFORMATIONS OF the basal ganglia and thalamus present a unique therapeutic challenge to the neurosurgeon given their unclear natural history, the risk of surgical treatment, and the unproven efficacy of radiosurgical therapy. Michiel Poorthuis See discussions, stats, and author profiles for this publication at: Catharina J M Klijn Retrieved on: To view Objective The reported effects of treating cerebral sions about CCM treatment rest upon indirect please visit the journal http: Two reviewers extracted data by identifying groups either at higher chance of a University Medical Center to quantify the incidence of a composite outcome good outcome or at lower risk of a poor outcome. The incidence of the composite outcome was risks of CCM treatment with neurosurgical excision Correspondence to 6. Neurosciences, University of median follow-up 4. We did Review and Meta-analyses guidelines. Long-term effects, especially eligibility criteria. We crosschecked the bibliograph- important for stereotactic radiosurgery, are unknown. If follow-up was ; J Neurol Neurosurg Psychiatry ; To assess consistency of effects across cohorts, we used the I-squared I2 statistic. We collected S1 including patients with treated CCM with a total of data on study design, patient demographics, CCM character- 10 patient-years of follow-up. Forty-nine cohorts involving istics, presenting symptoms and type of CCM treatment. We patients reported on neurosurgery patient-years of extracted data on whether each series reported consecutive or follow-up and 14 cohorts involving patients reported SRS selected patients, the method of follow-up prospective, retro- patient-years of follow-up with 11 using a Gamma spective, prospective patient collection with retrospective Knife10â 20 and 3 using a linear accelerator. Fourteen cohorts did were published before standards for reporting of CCM haemor- not describe mean nor median duration of follow-up, but only rhage were published. In none of the 63 cohorts was the outcome assessment performed by an independent Statistical analysis person, blinded to treatment. In the 14 cohorts reporting SRS We separated our analyses of cohorts according to whether outcome, the median margin dose was 16 range 12â 25 Gy they reported the effects of neurosurgical excision or SRS. Thirty-two cohorts reported on the composite outcome 21 patients, proportion of patients with a brainstem CCM, pro- neurosurgery cohorts and 11 SRS cohorts. The composite portion of patients with a prior symptomatic ICH from the outcome incidence was 6. We performed Poisson Associations with the composite outcome meta-regression analyses of cohort characteristics on the inci- In 22 cohorts with data on brainstem CCM, age, sex and pres- dence of the composite outcome. We assessed the 1. In 14 cohorts, after neurosurgical excision the adjusted relationship of cohort characteristics to each outcome by calcu- RR was 1. The incidence of the Poorthuis MHF, et al. ICH adjusted RR 0. We found that after neurosurgical excision or SRS the incidence of death, non-fatal symptomatic ICH or non-fatal new or worse Sensitivity analyses non-haemorrhagic persistent FND attributed to CCM or its We were not able to perform sensitivity analyses with high- treatment is around 6 per person-years. Poorthuis MHF, et al. For SRS we could not detect associations fatal stroke after both forms of treatment over 2â 3 years of with outcome. The period of 5 years, regardless of the CCM location. However, the short- follow-up of the studies included in the review was relatively term risks of treatment appear to compare favourably with the short, and the number of high-quality studies was too small to natural history of recurrent ICH We used a variety of statistical techniques safer over recent years including for brainstem CCMs28â 35, to account for the variation in reporting follow-up in individ- likely due to increasing surgical experience, technical develop- ual cohorts to maximise their inclusion ; the inclusion of out- ments and improved electrophysiological monitoring. Although the overall inci- 1, indicating the need for longer term follow-up in all studies dence of adverse effects after SRS was similar to neurosurgical reporting the effects of neurosurgical excision and SRS. Functional outcome after follow-up to capture the delayed effects of SRS. The lack scale 7 cohorts or by using a generic functional outcome of high-quality studies with long-term follow-up stresses the scale. Ideally, such cohorts ity to examine associations with outcome on any one generic Page 7

8 should include a randomised comparison of treatment versus scale. The overall risks of adverse events after neurosurgical excision or SRS may help to guide patient management by informing an Acknowledgements The authors are grateful to MW Boele and AS van der Heijden for their help with data acquisition. Reduction of hemorrhage risk after literature searches. MHFP searched bibliographies for additional articles. Minim Invasive Neurosurg ; Acta Academiae Medicinae Sinicae ; Gamma knife surgery for cavernous interpreted the data. J Neurosurg Suppl ; Stereotactic radiosurgery for deep-seated cavernous malformations: Gamma knife radiosurgery for intracranial Clinical Established Investigator grant T Clin Neurol Neurosurg ; Stereotactic radiosurgery in the management of angiographically occult vascular malformations. Seizure risk from cavernous or ; Stereotactic radiosurgery guidelines for the management of ; Prog Neurol Surg ; Microsurgical treatment of supratentorial cavernous cavernous malformations: Neurosurg Clin N Am ; Prospective hemorrhage risk of diagnosis and treatment of cerebral cavernous malformations in adults: Acta Neurochir Wien ; Preferred reporting items for systematic reviews stem. A review of cases. Surgical management of brain-stem cavernous 7 McCormick WF. The MRI appearance of cavernous brainstem: Measuring inconsistency in cavernomas. Radiosurgery for cavernous cavernomas: Treatment of symptomatic AOVMs with radiosurgery. Acta Neurochir Suppl ; Radiosurgery for cavernous malformations in basal ganglia, thalamus and microsurgical resection in 52 patients. Radiosurgery of intracranial cavernous approach to cavernous malformations of the brainstem: Surgical treatment of brainstem cavernous malformations. J Neurosurg ; Suppl: Surg Neurol ;72 Suppl 2: Supplementary Supplementary material can be found at: Sign up in the service box at the top right corner of the online article. Page 8

9 Chapter 5 : Surgical Strategies in Treating Brainstem Cavernous Malformations Neurosurgery Oxford Ac Radiosurgery for arteriovenous malformations of the basal ganglia, thalamus, and brainstem. Radiosur gery for arteriovenous malformations of the basal. radiosurgery of cavernous malformations. In 4 patients, permanent neurological deficits developed after surgery, while in the other 6, the deficits had resolved before last follow-up. The rate of permanent deficits after surgery was therefore 7. Five patients had surgery as their only treatment. The patient presented with sudden loss of consciousness. Axial CT image obtained at presentation, showing hemorrhage in the right basal ganglia. MR angiogram showing an AVM located just superior to the right M1 segment of the middle cerebral artery. The white arrow points to an enlarged lenticulostriate feeder. An early draining vein is seen on the medial aspect of the nidus white arrow. Lateral view of the AVM. The venous drainage into the basal vein of Rosenthal arrow and then to the straight sinus broken arrow is seen. This lesion was cured by surgery, via a conventional pterional craniotomy and transsylvian approach. The site of corticectomy was on the inferior frontal gyrus, just abutting the sylvian fissure black star, e. The hematoma and feeders to the nidus could be accessed via this approach. The hematoma has been evacuated, and the first of the lenticulostriate feeders is visible in the walls of the hematoma cavity arrow, f. Lesions that were obliterated were smaller in diameter 3. Similarly, inclusion of surgery OR 5. No other factors were associated with nidus obliteration. We generated Kaplan-Meier plots to display the probability of nidus obliteration over time; the Cox proportional hazards regression showed that only the inclusion of surgery significantly improved the probability of obliteration Fig. Kaplan-Meier graphs showing the probability of angiographic obliteration of the nidus over time. The graphs indicate the probability of angiographic obliteration over time, with respect to various dichotomized variables, including high grade A, received EVT B, received SRS C, and underwent surgery D. The p values listed in the figures are from a Cox proportional hazards regression to check for the significance of the differences between the 2 Kaplan-Meier lines in each plot. We then performed separate multivariate analyses for lower- and high-grade lesions. The mean follow-up was 9. At last follow-up, There was no correlation between pretreatment mrs score and outcome. Younger patients and those in the pediatric age group did worse than older adults; the mean age of patients who were worse at last follow-up was Location of the lesion influenced outcome; The maximum nidus diameter, AVM volume, and being high grade influenced outcome; venous drainage did not. No treatment modality appeared to influence outcome. We performed multivariate analysis using the factors already identified as correlating with outcome. Optimal Outcomes The best possible or optimal outcome was when a patient had a good clinical outcome see above and angiographic demonstration of obliteration of the AVM at last follow-up. The others, who had either a poor clinical outcome or persistent lesion at last follow-up, were classified as having suboptimal outcomes. Thus, our definition of optimal outcome included clinical as well as angiographic follow-up data; this complete data set was available for patients Table 4. Page 9