Seizure outcome after lesionectomy for cavernous malformations

1995 ◽  
Vol 83 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Douglas S. Cohen ◽  
Geoffrey P. Zubay ◽  
Robert R. Goodman
Keyword(s):  
Retrospective Analysis ◽  
Surgical Resection ◽  
Seizure Outcome ◽  
Cavernous Malformations ◽  
Content Type ◽  
Female Sex ◽  
Antiepileptic Medications ◽  
Fine Print

✓ Cavernous malformations that are associated with seizures are often treated by surgical resection consisting of lesion removal, “lesionectomy,” alone. Through retrospective analysis the authors have examined some factors that may predict failure to eradicate seizures by such a procedure. A group of 51 patients were examined who had been treated for supratentorial cavernous malformations with preoperative seizures and received postoperative follow up lasting at least 1 year. There was one mortality in the group. Of the remaining 50 patients, 15 (30%) had continued postoperative seizures despite therapeutic levels of antiepileptic medications. Variables that were significantly associated with continued seizures postoperatively included increasing duration of preoperative seizure history (p = 0.03), increasing number of preoperative seizures (p < 0.003), and female sex (p < 0.04). One hundred percent of patients with only one preoperative seizure or a seizure history lasting less than 2 months were seizure free following lesionectomy: approximately 75% to 80% of all patients with two to five seizures, or a seizure history lasting 2 to 12 months, were seizure free; and only 50% to 55% of those with more than five seizures or with preoperative seizure histories lasting more than 1 year were seizure free postoperatively. This investigation indicates that patients with shorter seizure histories and fewer preoperative seizures can be effectively treated by lesionectomy alone, whereas those with longer histories and more seizures are not effectively treated by this procedure and may require more extensive resections.

Long-term seizure outcomes following amygdalohippocampectomy

2003 ◽  
Vol 98 (4) ◽  
pp. 751-763 ◽  
Author(s):  
H. Gregor Wieser ◽  
Marcos Ortega ◽  
Alon Friedman ◽  
Yasuhiro Yonekawa
Keyword(s):  
Mesial Temporal Lobe Epilepsy ◽  
Outcome Data ◽  
University Hospital ◽  
Seizure Outcome ◽  
Content Type ◽  
Selective Amygdalohippocampectomy ◽  
Class 1 ◽  
Fine Print

Object. Analyses of the results of surgery for epilepsy are hindered by inconsistent classifications of seizure outcome, small numbers of patients, and short postoperative follow-up periods. The authors conducted a retrospective study with a reassessment of the long-term seizure outcomes in patients who underwent selective amygdalohippocampectomy (SelAH) for pharmacotherapy—resistant mesial temporal lobe epilepsy (MTLE) at the Zurich University Hospital from 1975 to 1999. Methods. Year-by-year data and the last available data on seizure outcomes were retrospectively assessed for 369 consecutively surgically treated patients who had participated in a follow-up period longer than 1 year as of 1999 and whose outcomes were classified according to the Engel scale and the proposed new International League Against Epilepsy (ILAE) scale. Patients were grouped into nonlesional and lesional MTLE groups depending on whether they harbored a gross anatomical lesion that caused the MTLE. Differentiation was made between curative and palliative operations. Complications related to surgery are reported for 453 patients who underwent SelAH and participated in more than 3 months of follow-up review. The last available outcome data according to the Engel scale were found to be generally similar to those of the new ILAE classification, with 66.9% of patients free from disabling seizures (Engel Class I) compared with 57.1% who were completely seizure and aura free (ILAE Class 1). The last available data on seizure outcome were not significantly different between patients in the lesional and nonlesional MTLE groups. In the lesional group, seizure outcomes were significantly better when patients underwent surgery early in the course of the disease. Overall, 70% of the patients received reductions in their antiepileptic drug treatment at the time of the last available follow-up review. Complications related to the surgical procedures were rare. Conclusions. The authors conclude that SelAH is a safe and effective surgical procedure for MTLE.

The natural history of familial cavernous malformations: results of an ongoing study

1994 ◽  
Vol 80 (3) ◽  
pp. 422-432 ◽  
Author(s):  
Joseph M. Zabramski ◽  
Thomas M. Wascher ◽  
Robert F. Spetzler ◽  
Blake Johnson ◽  
John Golfinos ◽  
...  
Keyword(s):  
Natural History ◽  
Mr Imaging ◽  
Ongoing Study ◽  
Mr Images ◽  
Cavernous Malformations ◽  
Content Type ◽  
Imaging Characteristics ◽  
Familial Form ◽  
Fine Print

✓ Cavernous malformations are congenital abnormalities of the cerebral vessels that affect 0.5% to 0.7% of the population. They occur in two forms: a sporadic form characterized by isolated lesions, and a familial form characterized by multiple lesions with an autosomal dominant mode of inheritance. The management of patients with cavernous malformations, particularly those with the familial form of the disease, remains a challenge because little is known regarding the natural history. The authors report the results of an ongoing study in which six families afflicted by familial cavernous malformations have been prospectively followed with serial interviews, physical examinations, and magnetic resonance (MR) imaging at 6- to 12-month intervals. A total of 59 members of these six families were screened for protocol enrollment; 31 (53%) had MR evidence of familial cavernous malformations. Nineteen (61%) of these 31 patients were symptomatic, with seizures in 12 (39%), recurrent headaches in 16 (52%), focal sensory/motor deficits in three (10%), and visual field deficits in two (6%). Twenty-one of these 31 patients underwent at least two serial clinical and MR imaging examinations. A total of 128 individual cavernous malformations (mean 6.5 ± 3.8 lesions/patient) were identified and followed radiographically. During a mean follow-up period of 2.2 years (range 1 to 5.5 years), serial MR images demonstrated 17 new lesions in six (29%) of the 21 patients; 13 lesions (10%) showed changes in signal characteristics, and five lesions (3.9%) changed significantly in size. The incidence of symptomatic hemorrhage was 1.1% per lesion per year. The results of this study demonstrate that the familial form of cavernous malformations is a dynamic disease; serial MR images revealed changes in the number, size, and imaging characteristics of lesions consistent with acute or resolving hemorrhage. It is believed that the de novo development of new lesions in this disease has not been previously reported. These findings suggest that patients with familial cavernous malformations require careful follow-up monitoring, and that significant changes in neurological symptoms warrant repeat MR imaging. Surgery should be considered only for lesions that produce repetitive or progressive symptoms. Prophylactic resection of asymptomatic lesions does not appear to be indicated.

Seizure outcome in patients with surgically treated cerebral arteriovenous malformations

1993 ◽  
Vol 78 (1) ◽  
pp. 5-11 ◽  
Author(s):  
David G. Piepgras ◽  
Thoralf M. Sundt ◽  
Ashvin T. Ragoonwansi ◽  
Lorna Stevens
Keyword(s):  
Arteriovenous Malformations ◽  
The United States ◽  
Seizure Disorder ◽  
Seizure Outcome ◽  
Cerebral Arteriovenous Malformations ◽  
Content Type ◽  
Follow Up Study ◽  
Significant Difference ◽  
Fine Print

✓ A series of 280 cases of cerebral arteriovenous malformations (AVM's) treated surgically between June, 1970, and June, 1989, is reviewed with particular focus on the preoperative seizure history and follow-up seizure status. Follow-up evaluation (mean duration 7.5 years) was achieved in 98% of cases and was accomplished through re-examinations, telephone interviews, and written questionnaires. Overall, 89% of the surviving patients with a follow-up period of greater than 2 years were free of seizures at last examination. Of the 280 patients in this series. 163 had experienced no seizures preoperatively. A recent follow-up study (with a minimum duration of 2 years or to death) was available in 157 of these 163 cases; 21 patients had died. Of the 136 surviving patients, only eight (6%) were having new ongoing seizures. In the 128 (94%) who had remained seizure-free, 73% were receiving no anticonvulsant agents while 27% were taking anticonvulsant prophylaxis. The 2-year minimum follow-up study in 110 of the 117 patients with preoperative seizures revealed that eight (7%) had died. Of the 102 surviving patients, 85 (83%) were seizure-free (with 48% no longer receiving anticonvulsant therapy), while 17 (17%) still suffered intermittent seizures. However, of these 17 patients, 13 reported their seizures to be improved compared to preoperatively; the seizures were the same in two patients and were worse in two patients. An actuarial analysis was conducted comparing the life expectancy of patients following surgery for AVM's with the expected survival of a general white population of the same age and sex in the West Northcentral region of the United States. No statistically significant difference was found. There were seven perioperative deaths (three from cerebral hemorrhage, two from pulmonary emboli, and two from obstruction of venous drainage) and 22 deaths during the follow-up period. Of these 22 deaths, the cause was unknown in four patients, apparently unrelated to the AVM in 13, and directly or indirectly related to the patient's neurological condition prior to surgery or due to surgery performed for resection of the AVM in five. There was a statistically significant relationship between the size and location of the AVM and the clinical presentation. Patients with small AVM's (< 3 cm) were more likely to present with hemorrhage whereas those with large AVM's were more likely to present with seizures. Conclusions from this study are: 1) there is a low incidence of a new seizure disorder following surgery: 2) chances for resolution or control of a pre-existing seizure disorder are good: 3) although resolution of seizures or seizure control was achieved postoperatively in AVM's of all sizes, this benefit was highest in smaller as opposed to larger AVM's; and 4) ultimately, there is a good capacity for recovery from pre-existing neurological deficits or those resulting from surgery.

Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage

1997 ◽  
Vol 87 (2) ◽  
pp. 190-197 ◽  
Author(s):  
Phillip J. Porter ◽  
Robert A. Willinsky ◽  
William Harper ◽  
M. Christopher Wallace
Keyword(s):  
Natural History ◽  
Cerebellar Nuclei ◽  
Neurological Deterioration ◽  
Focal Neurological Deficit ◽  
Cavernous Malformations ◽  
Content Type ◽  
Lesion Location ◽  
Neurological Event ◽  
Fine Print

✓ Despite recent studies of the natural history of cavernous malformations, there remains significant uncertainty concerning hemorrhage rates and the importance of lesion location. Controversy arises over varying definitions of “hemorrhage.” What is ultimately important to the patient is the occurrence of a neurological event, which may or may not be associated with radiologically documented hemorrhage, as well as the chance of recovery after such an event. The purpose of this study was to determine the rates of occurrence and sequelae of neurological events in 173 patients referred to our vascular malformation clinic with cavernous malformations. All patient data were entered into a database. The mean age at presentation for the 173 patients was 37.5 years. The lesion location was deep (brainstem, cerebellar nuclei, thalamus, or basal ganglia) in 64 patients (37%) and superficial in 109 (63%). Thirty-one patients (18%) had multiple lesions. Disease presentation was due to seizures in 62 patients (36%), hemorrhage in 44 (25%), focal neurological deficit without documented hemorrhage in 35 (20%), headache alone in 11 (6%), and incidental findings in 21 patients (12%). The results obtained in the 110 patients eligible for follow-up review were used to derive information on the rates of hemorrhage and neurological events. An interval event (neurological deterioration) required both symptoms and signs. The total mean follow-up period was 46 months, the majority (65%) of which was prospective. There were 18 interval events in 427 patient-years of follow-up review, for an overall annual event rate of 4.2%. Location was the most important factor for predicting interval event occurrence, with significantly higher rates for deeply located (10.6%/year) compared with superficially located lesions (0%/year) (p = 0.0001). Of patients suffering a neurological event, only 37% had complete resolution of their deficits. This largely prospective study indicates that deep cavernous malformations carry a worse prognosis than superficial lesions with respect to annual rates of neurological deterioration. The alarming rate of adverse clinical events occurring in patients with deep lesions is punctuated by the fact that less than one-half of them recover fully during long-term follow-up review.

Cavernous malformations of the brainstem: experience with 100 patients

1999 ◽  
Vol 90 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Randall W. Porter ◽  
Paul W. Detwiler ◽  
Robert F. Spetzler ◽  
Michael T. Lawton ◽  
Jonathan J. Baskin ◽  
...  
Keyword(s):  
Natural History ◽  
Skull Base ◽  
Surgical Patients ◽  
Cavernous Malformations ◽  
Content Type ◽  
History Of ◽  
Lost To Follow Up ◽  
Pontomedullary Junction ◽  
Fine Print

Object. In this study the authors review surgical experience with cavernous malformations of the brainstem (CMBs) in an attempt to define more clearly the natural history, indications, and risks of surgical management of these lesions.Methods. The authors retrospectively reviewed the cases of 100 patients (38 males and 62 females; mean age 37 years) harboring 103 lesions at treated a single institution between 1984 and 1997. Clinical histories, radiographs, pathology records, and operative reports were evaluated. The brainstem lesions were distributed as follows: pons in 39 patients, medulla in 16, midbrain in 16, pontomesencephalic junction in 15, pontomedullary junction in 10, midbrain—hypothalamus/thalamus region in two patients, and more than two brainstem levels in five. The retrospective annual hemorrhage rate was most conservatively estimated at 5% per lesion per year. Standard skull base approaches were used to resect lesions in 86 of the 100 patients. Intraoperatively, all 86 patients were found to have a venous anomaly in association with the CMB. Follow up was available in 98% (84 of 86) of the surgical patients. Of these, 73 (87%) were the same or better after surgical intervention, eight (10%) were worse, and three (4%) died. Two surgical patients were lost to follow-up review. Incidences of permanent or severe morbidity occurred in 10 (12%) of the surgically treated patients. The average postoperative Glasgow Outcome Scale score for surgically treated patients was 4.5, with a mean follow-up period of 35 months.Conclusions. The natural history of CMBs is worse than that of cavernous malformations in other locations. These CMBs can be resected using skull base approaches, which should be considered in patients with symptomatic hemorrhage who harbor lesions that approach the pial surface. Venous anomalies are always associated with CMBs and must be preserved.

Dynamic nature of cavernous malformations: a prospective magnetic resonance imaging study with volumetric analysis

2000 ◽  
Vol 93 (6) ◽  
pp. 981-986 ◽  
Author(s):  
Richard E. Clatterbuck ◽  
John L. Moriarity ◽  
Ilhan Elmaci ◽  
Roland R. Lee ◽  
Steven N. Breiter ◽  
...  
Keyword(s):  
Mr Imaging ◽  
De Novo ◽  
Volume Data ◽  
Mr Images ◽  
Cavernous Malformations ◽  
Content Type ◽  
Signal Characteristics ◽  
The Mean ◽  
Fine Print

Object. Although cavernous malformations (CMs) are not detected in angiographic studies, they have a characteristic appearance on magnetic resonance (MR) images. A number of reports published in the last decade have focused on the behavior of these lesions within the clinical environment. However, little has been published about the evolution of CMs over time, as observed in imaging studies. To understand imaging-documented changes in CMs over time, we analyzed MR images of 114 cavernous malformations in 68 patients who were followed prospectively.Methods. For each CM the location, volume, and MR imaging signal characteristics were recorded. Volume data were available for 107 lesions from initial images. The mean volume of these 107 CMs was 2779 mm3. The lesions ranged in size from 0.5 to 46,533 mm3 (46.5 cm3). Volume data from a second set of images were available for 76 CMs (mean interval from first imaging session 26 months), and from a third set of images for 24 lesions (mean interval from second imaging session 18 months). Over the first follow-up interval, the mean volume change was −991 mm3 (a decrease of approximately 1 cm3) and over the second interval the mean volume change was −642 mm3. Although these mean volume changes appear modest, volume changes in single lesions during follow-up intervals were more dramatic, with decreases as large as 45,629 mm3 (45.6 cm3) and increases as large as 6,074 mm3 (6 cm3). Serial examinations of the MR imaging signal characteristics of these CMs demonstrate a trend for maturation of blood products from a subacute, to a mixed, and finally to a chronic appearance. Three lesions appeared de novo during the follow-up period.Conclusions. On the basis of their analysis, the authors conclude that CMs exhibit a range of dynamic behaviors including enlargement, regression, and de novo formation, as well as progression through a series of characteristic MR imaging appearances.

Management of intracranial plasmacytoma

1995 ◽  
Vol 83 (2) ◽  
pp. 218-221 ◽  
Author(s):  
Ajay K. Bindal ◽  
Rajesh K. Bindal ◽  
Harry van Loveren ◽  
Raymond Sawaya
Keyword(s):  
Multiple Myeloma ◽  
Radiation Therapy ◽  
Skull Base ◽  
Surgical Resection ◽  
Postoperative Period ◽  
Definitive Treatment ◽  
Content Type ◽  
Complete Surgical Resection ◽  
Fine Print

✓ The authors report on a study of eight cases of intracranial plasmacytoma to identify the risk of progression to multiple myeloma and suggest the treatment required for cure of solitary lesions. The diagnosis of multiple myeloma or myelomatous changes was made in the immediate postoperative period in four patients (50%), two of whom had skull base lesions. Of the four remaining patients, three were treated with complete surgical resection and radiation therapy and had no recurrence of plasmacytoma or progression to multiple myeloma during mean follow up of 12 years (range 2–25 years); one patient underwent subtotal surgical resection and had recurrence of the tumor despite radiation therapy. It is concluded that multiple myeloma is unlikely to develop during the long term in patients with intracranial plasmacytoma who do not develop multiple myeloma or myelomatous changes in the early postoperative period. However, lesions that infiltrate the skull base are not likely to be solitary, and patients who harbor these neoplasms should undergo complete evaluation and close follow-up review to exclude multiple myeloma. A recurrence of solitary intracranial plasmacytoma is possible with subtotal surgical resection despite radiation therapy. Definitive treatment should consist of complete surgical resection with adjuvant radiation therapy.

The natural history of cerebral cavernous malformations

1995 ◽  
Vol 83 (5) ◽  
pp. 820-824 ◽  
Author(s):  
Douglas Kondziolka ◽  
L. Dade Lunsford ◽  
John R. W. Kestle
Keyword(s):  
Natural History ◽  
Management Strategies ◽  
Operative Management ◽  
Neurological Deficits ◽  
Cavernous Malformations ◽  
Content Type ◽  
Increased Risk ◽  
History Of ◽  
Fine Print

✓ To determine the natural history of brain cavernous malformations, the authors entered patients referred to their center into a prospective registry between 1987 and 1993. All patients underwent magnetic resonance imaging, which showed the typical appearance of this lesion, and conservative management was recommended in all. Patients or their referring physicians were contacted for follow-up data. The purpose of the study was to define the rate of symptomatic hemorrhage and to determine the outcome in those patients who had suffered seizures. Follow-up data were available for 122 patients with a mean age at entry of 37 years (range 4–82 years). The malformation was located in the brainstem in 43 cases (35%), the basal ganglia/thalamus in 20 (17%), and a hemispheric area in 59 (48%). Fifty percent of patients had never had a symptomatic hemorrhage, 41% had one bleed, 7% had two, and 2% had three. Seizures were reported in 23% of patients and headaches in 15%. Lesions were solitary in 80% of patients and multiple in 20%. The retrospective annual hemorrhage rate (61 bleeds/4550.6 patient-years of life) was 1.3%. The mean prospective follow-up period was 34 months. There were nine bleeds during this time, six with new neurological deficits. In patients without a prior bleed, the prospective annual rate of hemorrhage was 0.6%. In contrast, patients with prior hemorrhage had an annual bleed rate of 4.5% (p = 0.028). Patient sex (p = 0.97) or the presence of seizures (p = 0.11), headaches (p = 0.06), or solitary versus multiple lesions (p = 0.15) were not significant predictors of later hemorrhage. There was no difference in the rate of bleeds between brain locations. Four patients with seizures became seizurefree and four patients without seizures later developed seizures; only one patient developed intractable seizures. Fourteen patients (11%) underwent surgery (two after hemorrhage, five with seizures, and seven with progressive deficits), and five had radiosurgery. No patient died in the follow-up period. This study indicates that conservative versus operative management strategies may need to be redefined, especially in patients who present with hemorrhage and who appear to have a significantly increased risk of subsequent rehemorrhage.

Evaluation of gamma thalamotomy for parkinsonian and other tremors: survival of neurons adjacent to the thalamic lesion after gamma thalamotomy

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 120-127 ◽  
Author(s):  
Chihiro Ohye ◽  
Tohru Shibazaki ◽  
Junji Ishihara ◽  
Jie Zhang
Keyword(s):  
Tissue Reaction ◽  
Vascular Lesions ◽  
Thalamic Lesion ◽  
Mr Images ◽  
Unsatisfactory Result ◽  
Content Type ◽  
Rhythmic Discharge ◽  
Latent Interval ◽  
Fine Print

Object. The effects of gamma thalamotomy for parkinsonian and other kinds of tremor were evaluated. Methods. Thirty-six thalamotomies were performed in 31 patients by using a 4-mm collimator. The maximum dose was 150 Gy in the initial six cases, which was reduced to 130 Gy thereafter. The longest follow-up period was 6 years. The target was determined on T2-weighted and proton magnetic resonance (MR) images. The point chosen was in the lateral-most part of the thalamic ventralis intermedius nucleus. This is in keeping with open thalamotomy as practiced at the authors' institution. In 15 cases, gamma thalamotomy was the first surgical procedure. In other cases, previous therapeutic or vascular lesions were visible to facilitate targeting. Two types of tissue reaction were onserved on MR imaging: a simple oval shape and a complex irregular shape. Neither of these changes affected the clinical course. In the majority of cases, the tremor subsided after a latent interval of approximately 1 year after irradiation. The earliest response was demonstrated at 3 months. In five cases the tremor remained. In four of these cases, a second radiation session was administered. One of these four patients as well as another patient with an unsatisfactory result underwent open thalamotomy with microrecording. In both cases, depth recording adjacent to the necrotic area revealed normal neuronal activity, including the rhythmic discharge of tremor. Minor coagulation was performed and resulted in immediate and complete arrest of the remaining tremor. Conclusions. Gamma thalamotomy for Parkinson's disease seems to be an alternative useful method in selected cases.

Gamma knife radiosurgery as a single treatment modality for large cerebral arteriovenous malformations

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 113-119 ◽  
Author(s):  
D. Hung-Chi Pan ◽  
Wan-Yuo Guo ◽  
Wen-Yuh Chung ◽  
Cheng-Ying Shiau ◽  
Yue-Cune Chang ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Arteriovenous Malformations ◽  
Radiation Treatment ◽  
Gamma Knife Radiosurgery ◽  
Consecutive Series ◽  
Content Type ◽  
Obliteration Rate ◽  
Complete Obliteration ◽  
Fine Print

Object. A consecutive series of 240 patients with arteriovenous malformations (AVMs) treated by gamma knife radiosurgery (GKS) between March 1993 and March 1999 was evaluated to assess the efficacy and safety of radiosurgery for cerebral AVMs larger than 10 cm3 in volume. Methods. Seventy-six patients (32%) had AVM nidus volumes of more than 10 cm3. During radiosurgery, targeting and delineation of AVM nidi were based on integrated stereotactic magnetic resonance (MR) imaging and x-ray angiography. The radiation treatment was performed using multiple small isocenters to improve conformity of the treatment volume. The mean dose inside the nidus was kept between 20 Gy and 24 Gy. The margin dose ranged between 15 to 18 Gy placed at the 55 to 60% isodose centers. Follow up ranged from 12 to 73 months. There was complete obliteration in 24 patients with an AVM volume of more than 10 cm3 and in 91 patients with an AVM volume of less than 10 cm3. The latency for complete obliteration in larger-volume AVMs was significantly longer. In Kaplan—Meier analysis, the complete obliteration rate in 40 months was 77% in AVMs with volumes between 10 to 15 cm3, as compared with 25% for AVMs with a volume of more than 15 cm3. In the latter, the obliteration rate had increased to 58% at 50 months. The follow-up MR images revealed that large-volume AVMs had higher incidences of postradiosurgical edema, petechiae, and hemorrhage. The bleeding rate before cure was 9.2% (seven of 76) for AVMs with a volume exceeding 10 cm3, and 1.8% (three of 164) for AVMs with a volume less than 10 cm3. Although focal edema was more frequently found in large AVMs, most of the cases were reversible. Permanent neurological complications were found in 3.9% (three of 76) of the patients with an AVM volume of more than 10 cm3, 3.8% (three of 80) of those with AVM volume of 3 to 10 cm3, and 2.4% (two of 84) of those with an AVM volume less than 3 cm3. These differences in complications rate were not significant. Conclusions. Recent improvement of radiosurgery in conjunction with stereotactic MR targeting and multiplanar dose planning has permitted the treatment of larger AVMs. It is suggested that gamma knife radiosurgery is effective for treating AVMs as large as 30 cm3 in volume with an acceptable risk.

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