scholarly journals Cerebral cavernous malformations and epilepsy

2006 ◽  
Vol 21 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Issam Awad ◽  
Pascal Jabbour
Keyword(s):  
Natural History ◽  
Therapeutic Intervention ◽  
Clinical Manifestations ◽  
Neurological Deficits ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Chronic Epilepsy ◽  
Seizure Disorders ◽  
Similar Lesion ◽  
Clinically Significant

✓Seizures and epilepsy are frequent clinical manifestations of cerebral cavernous malformations (CCMs) and represent the most common symptomatic presentation of supratentorial lesions. Clinicians often diagnose CCMs in patients after a first seizure, or in some cases after obtaining neuroimaging studies in patients suffering from chronic epilepsy previously thought to be idiopathic. In some cases, the lesion is clinically significant solely because of its epileptogenicity, but in others there may be concern about potential hemorrhage or focal neurological deficits from a similar lesion. The authors present current pathophysiological concepts related to epilepsy associated with CCMs. They discuss the spectrum of seizure disorders associated with these lesions and review the natural history, prognosis, and options for therapeutic intervention.

Coexistence of intracranial and spinal cavernous malformations: a study of prevalence and natural history

2006 ◽  
Vol 104 (3) ◽  
pp. 376-381 ◽  
Author(s):  
Aaron A. Cohen-Gadol ◽  
Jeffrey T. Jacob ◽  
Diane A. Edwards ◽  
William E. Krauss
Keyword(s):  
Family History ◽  
Natural History ◽  
Mr Imaging ◽  
Neurological Deficits ◽  
Cavernous Malformations ◽  
Recurrent Hemorrhage ◽  
Long Term Follow Up ◽  
History Of ◽  
Clinically Significant

Object The purpose of this study was to examine the prevalence of intracranial cavernous malformations (CMs) in a large series of predominantly Caucasian patients with spinal cord CMs. The authors also studied the natural history of spinal CMs in patients who were treated nonoperatively. Methods The medical records of 67 consecutive patients (32 female and 35 male patients) in whom a spinal CM was diagnosed between 1994 and 2002 were reviewed. The patients’ mean age at presentation was 50 years (range 13–82 years). Twenty-five patients underwent resection of the lesion. Forty-two patients in whom the spinal CM was diagnosed using magnetic resonance (MR) imaging were followed expectantly. Thirty-three (49%) of 67 patients underwent both spinal and intracranial MR imaging. All available imaging studies were reviewed to determine the coexistence of an intracranial CM. Fourteen (42%) of the 33 patients with spinal CMs who underwent intracranial MR imaging harbored at least one cerebral CM in addition to the spinal lesion. Six (43%) of these 14 patients did not have a known family history of CM. Data obtained during the long-term follow-up period (mean 9.7 years, total of 319 patient-years) were available for 33 of the 42 patients with a spinal CM who did not undergo surgery. Five symptomatic lesional hemorrhages (neurological events), four of which were documented on neuroimaging studies, occurred during the follow-up period, for an overall event rate of 1.6% per patient per year. No patient experienced clinically significant neurological deficits due to recurrent hemorrhage. Conclusions As many as 40% of patients with a spinal CM may harbor a similar intracranial lesion, and approximately 40% of patients with coexisting spinal and intracranial CMs may have the nonfamilial (sporadic) form of the disease. Patients with symptomatic spinal CMs who are treated nonoperatively may have a small risk of clinically significant recurrent hemorrhage. The findings will aid in evaluation of surveillance images and in counseling of patients with spinal CMs, irrespective of family history.

scholarly journals The natural history of cerebral cavernous malformations in children

2016 ◽  
Vol 17 (2) ◽  
pp. 123-128 ◽  
Author(s):  
Bradley A. Gross ◽  
Rose Du ◽  
Darren B. Orbach ◽  
R. Michael Scott ◽  
Edward R. Smith
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Natural History ◽  
Significant Risk ◽  
Neurological Deficits ◽  
Cerebral Cavernous Malformations ◽  
Similar Data ◽  
Cavernous Malformations ◽  
Neurological Morbidity ◽  
History Of

OBJECT Cerebral cavernous malformations (CMs) are a source of neurological morbidity from seizures and focal neurological deficits due to mass effect and hemorrhage. Although several natural history reports exist for adults with CMs, similar data for pediatric patients are limited. METHODS The authors reviewed hospital databases to identify children with CMs who had not been treated surgically and who had clinical and radiological follow-up. Annual hemorrhage rates were calculated in lesion-years, and risk factors were assessed using the Cox proportional hazards model. RESULTS In a cohort of 167 patients with 222 CMs, the mean patient age at the time of diagnosis was 10.1 years old (SD 6.0). Ninety patients (54%) were male. One hundred four patients (62%) presented with hemorrhage from at least 1 CM, 58 (35%) with seizures with or without CM hemorrhage, and 43 (26%) with incidental lesions. Twenty-five patients (15%) had multiple CMs, 17 (10%) had a family history of CMs, and 33 (20%) had radiologically apparent developmental venous anomalies (DVAs). The overall annual hemorrhage rate was 3.3%. Permanent neurological morbidity was 29% per hemorrhage, increasing to 45% for brainstem, thalamic, or basal ganglia CM and decreasing to 15% for supratentorial lobar or cerebellar lesions. The annual hemorrhage rate for incidental CMs was 0.5%; for hemorrhagic CMs, it was 11.3%, increasing to 18.2% within the first 3 years. Hemorrhage clustering within 3 years was statistically significant (HR 6.1, 95% CI 1.72–21.7, p = 0.005). On multivariate analysis, hemorrhagic presentation (HR 4.63, 95% CI 1.53–14.1, p = 0.007), brainstem location (HR 4.42, 95% CI 1.57–12.4, p = 0.005), and an associated radiologically apparent DVA (HR 2.91, 95% CI 1.04–8.09, p = 0.04) emerged as significant risk factors for hemorrhage, whereas age, sex, CM multiplicity, and CM family history did not. CONCLUSIONS Prior hemorrhage, brainstem location, and associated DVAs are significant risk factors for symptomatic hemorrhage in children with CMs. Hemorrhage clustering within the first 3 years of a bleed can occur, a potentially important factor in patient management and counseling.

scholarly journals Natural history and treatment options of radiation-induced brain cavernomas: a systematic review

2021 ◽  
Author(s):  
Gildas Patet ◽  
Andrea Bartoli ◽  
Torstein R. Meling
Keyword(s):  
Systematic Review ◽  
Natural History ◽  
Radiation Treatment ◽  
Neurological Deficits ◽  
Cochrane Library ◽  
Average Dose ◽  
Cavernous Malformations ◽  
Radiation Induced ◽  
The Mean

AbstractRadiation-induced cavernous malformations (RICMs) are delayed complications of brain irradiation during childhood. Its natural history is largely unknown and its incidence may be underestimated as RCIMS tend to develop several years following radiation. No clear consensus exists regarding the long-term follow-up or treatment. A systematic review of Embase, Cochrane Library, PubMed, Google Scholar, and Web of Science databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed. Based on our inclusion/exclusion criteria, 12 articles were included, totaling 113 children with RICMs, 86 were treated conservatively, and 27 with microsurgery. We were unable to precisely define the incidence and natural history from this data. The mean age at radiation treatment was 7.3 years, with a slight male predominance (54%) and an average dose of 50.0 Gy. The mean time to detection of RICM was 9.2 years after radiation. RICM often developed at distance from the primary lesion, more specifically frontal (35%) and temporal lobe (34%). On average, 2.6 RICMs were discovered per child. Sixty-seven percent were asymptomatic. Twenty-one percent presented signs of hemorrhage. Clinical outcome was favorable in all children except in 2. Follow-up data were lacking in most of the studies. RICM is most often asymptomatic but probably an underestimated complication of cerebral irradiation in the pediatric population. Based on the radiological development of RICMs, many authors suggest a follow-up of at least 15 years. Studies suggest observation for asymptomatic lesions, while surgery is reserved for symptomatic growth, hemorrhage, or focal neurological deficits.

scholarly journals Supratentorial cerebral cavernous malformations: clinical, surgical, and genetic involvement

2006 ◽  
Vol 21 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Vincenzo Antonio D'Angelo ◽  
Costanzo De Bonis ◽  
Rosina Amoroso ◽  
Alessandro Calì ◽  
Leonardo D'Agruma ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Family Members ◽  
Neurological Deficits ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Psychological Burden ◽  
Management Algorithm ◽  
Screening Protocol

Object Although there is general agreement on the methods of treatment for symptomatic supratentorial cerebral cavernous malformations (CMs) located in noneloquent areas, some controversy exists regarding the management of cerebral CMs that are asymptomatic and/or located in eloquent or deep areas. Moreover, recent advances in genetic findings could influence both standard clinical management and the follow-up strategy in affected individuals. Thus, the objective of this study was to develop, based on the authors' experience and a literature review, a management algorithm to deal with supratentorial cerebral CMs. Methods The authors retrospectively reviewed the clinical data related to 118 patients who underwent surgery for symptomatic supratentorial cerebral CMs at their institution. Twenty-eight of 118 patients harbored multiple lesions, and nine of these 28 patients had a clinically positive familial history. Genetic investigations were performed in 89 patients (75%). Conclusions Surgery for supratentorial cerebral CMs in noneloquent locations is safe and curative. In cerebral CMs located in deep and eloquent areas and with symptoms including progressive neurological deficits, evidence of hemorrhage, and uncontrolled seizures, surgical treatment according to an integrated plan based on frameless stereotactic guidance and functional magnetic resonance imaging is recommended and results in acceptably low morbidity. The data support the need for long-term imaging follow up in all patients, careful preoperative vascular studies to detect associated venous anomalies, and the importance of genetic mutational analysis. The DNA screening protocol will change the care of family members of patients with familial forms of cerebral CMs, because affected asymptomatic family members may benefit by early detection of lesions. At the same time, the exclusion of family members who are not carriers of the mutation as members of the population at risk reduces the economic and psychological burden of clinical and instrumental monitoring.

Oligoclonal immune response in cerebral cavernous malformations

2007 ◽  
Vol 107 (5) ◽  
pp. 1023-1026 ◽  
Author(s):  
Changbin Shi ◽  
Robert Shenkar ◽  
H. Hunt Batjer ◽  
Irene J. Check ◽  
Issam A. Awad
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Isoelectric Focusing ◽  
Clinical Manifestations ◽  
Normal Brain ◽  
Cerebral Cavernous Malformations ◽  
Blood Contamination ◽  
Cavernous Malformations ◽  
Control Brain ◽  
Potential Marker

Object Mechanisms of cerebral cavernous malformation (CCM) pathogenesis include genetic predisposition in some cases, but other factors are likely to be involved in lesion proliferation and clinical manifestations. Given the unique antigenic milieu of CCMs, there may be a characteristic immune response in these lesions. We hypothesize that the immunoglobulin (Ig) fraction in CCMs reflects an oligoclonal immune response not present in paired sera from the same patients or in other types of cerebrovascular malformations. Methods Surgically excised lesions from five patients with CCMs, three patients with arteriovenous malformations (AVMs), and four normal brain control specimens obtained at autopsy were homogenized and extract tested for IgG clonality by isoelectric focusing in parallel with each patient's serum. Results The authors detected B cells in all three lesions examined, and plasmacytes in two out of three lesions examined. Four of five extracts of homogenized CCMs showed an oligoclonal pattern of IgG distinct from the polyclonal pattern seen in those patients' sera. Immununoglobulin G oligoclonality was not seen in AVMs or control brain specimens. Conclusions The results of isoelectric focusing studies showed that CCM lesions had oligoclonal patterns of IgG unrelated to peripheral blood contamination, indicating selective synthesis of IgG within the lesions. This finding probably reflects a clonal expansion of B cells and/or plasmacytes in CCMs, an event that might be antigen-driven or a potential marker of inflammation.

Effective surgical treatment of cerebral cavernous malformations: a multicenter study of 79 pediatric patients

2011 ◽  
Vol 8 (5) ◽  
pp. 522-525 ◽  
Author(s):  
Michael Hugelshofer ◽  
Nicola Acciarri ◽  
Ulrich Sure ◽  
Dimitrios Georgiadis ◽  
Ralf W. Baumgartner ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Refractory Epilepsy ◽  
Epileptic Seizures ◽  
Neurological Deficits ◽  
Vascular Lesions ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Persistent Symptoms ◽  
The Mean ◽  
The Brain

Object Cerebral cavernous malformations (CCMs) are common vascular lesions in the brain, affecting approximately 0.5% of the population and representing 10%–20% of all cerebral vascular lesions. One-quarter of all CCMs affect pediatric patients, and CCMs are reported as one of the main causes of brain hemorrhage in this age group. Symptoms include epileptic seizures, headache, and focal neurological deficits. Patients with symptomatic CCMs can be treated either conservatively or with resection if lesions cause medically refractory epilepsy or other persistent symptoms. Methods The authors retrospectively analyzed 79 pediatric patients (41 boys and 38 girls) from 3 different centers, who were surgically treated for their symptomatic CCMs between 1974 and 2004. The mean age of the children at first manifestation was 9.7 years, and the mean age at operation was 11.3 years. The main goal was to compare the clinical outcomes with respect to the location of the lesion of children who preoperatively suffered from epileptic seizures. Results Of these patients, 77.3% were seizure free (Engel Class I) after the resection of the CCM. Significant differences in the outcome between children who harbored CCMs at different locations were not found. Conclusions Resection seems to be the favorable treatment of symptomatic CCMs not only in adults but also in children.

scholarly journals The pathogenetic features of cerebral cavernous malformations: a comprehensive review with therapeutic implications

2010 ◽  
Vol 29 (3) ◽  
pp. E2 ◽  
Author(s):  
Khaled M. Krisht ◽  
Kevin J. Whitehead ◽  
Toba Niazi ◽  
William T. Couldwell
Keyword(s):  
Neurological Deficits ◽  
Therapeutic Modality ◽  
Vascular Lesions ◽  
Cerebral Cavernous Malformations ◽  
Mice Model ◽  
Genetic Studies ◽  
Cavernous Malformations ◽  
Therapeutic Implications ◽  
Model Studies ◽  
Shed Light

Cerebral cavernous malformations (CCMs) are common vascular lesions of the CNS that may lead to seizures, focal neurological deficits, and fatal hemorrhagic stroke. Human genetic studies have identified 3 genes associated with CCM, and biochemical and molecular studies in mice have elucidated signaling pathways with important therapeutic implications. In this review, the authors shed light on the 3 discovered CCM genes as well as their protein products, with particular emphasis on their signal transduction pathways and their interaction with one another. Close focus is directed at mice model studies involving the Ccm2 gene product signaling pathway, revealing an important role for the use of simvastatin or other RhoA inhibitors as a therapeutic modality in the treatment of CCM. The remaining challenges to creating a more faithful CCM animal model as well as future clinical and research implications are reviewed.

Stereotactic radiosurgery for symptomatic solitary cerebral cavernous malformations considered high risk for resection

2010 ◽  
Vol 113 (1) ◽  
pp. 23-29 ◽  
Author(s):  
L. Dade Lunsford ◽  
Aftab A. Khan ◽  
Ajay Niranjan ◽  
Hideyuki Kano ◽  
John C. Flickinger ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Stereotactic Radiosurgery ◽  
Radiation Effects ◽  
Brain Structures ◽  
Neurological Deficits ◽  
Surgical Removal ◽  
Cerebral Cavernous Malformations ◽  
Safe Procedure ◽  
Cavernous Malformations ◽  
Risk Of Hemorrhage

Object A retrospective study was conducted to reassess the benefit and safety of stereotactic radiosurgery (SRS) in patients with solitary cerebral cavernous malformations (CCMs) that bleed repeatedly and are poor candidates for surgical removal. Methods Between 1988 and 2005 at the University of Pittsburgh, the authors performed SRS in 103 evaluable patients (57 males and 46 females) with solitary symptomatic CCMs. The mean patient age was 39.3 years. Ninety-eight percent of these patients had experienced 2 or more hemorrhages associated with new neurological deficits. Seventeen patients (16.5%) had undergone attempted resection before radiosurgery. Ninety-three CCMs were located in deep brain structures and 10 were in subcortical lobar areas of functional brain importance. The median malformation volume was 1.31 ml, and the median tumor margin dose was 16 Gy. Results The follow-up ranged from 2 to 20 years. The annual hemorrhage rate—that is, a new neurological deficit associated with imaging evidence of a new hemorrhage—before SRS was 32.5%. After SRS 22 hemorrhages were observed within 2 years (10.8% annual hemorrhage rate) and 4 hemorrhages were observed after 2 years (1.06% annual hemorrhage rate). The risk of hemorrhage from a CCM was significantly reduced after radiosurgery (p < 0.0001). Overall, new neurological deficits due to adverse radiation effects following SRS developed in 14 patients (13.5%), with most occurring early in our experience. Modifications in technique (treatment volume within the T2-weighted MR imaging–defined margin, use of MR imaging, and dose reduction for CCM in critical brainstem locations) further reduced risks after SRS. Conclusions Data in this study provide further evidence that SRS is a relatively safe procedure that reduces the rebleeding rate for CCMs located in high-surgical-risk areas of the brain.

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