Prospective follow-up of 33 asymptomatic patients with familial cerebral cavernous malformations

Neurology ◽  
2001 ◽  
Vol 57 (10) ◽  
pp. 1825-1828 ◽  
Author(s):  
P. Labauge ◽  
L. Brunereau ◽  
S. Laberge ◽  
J.-P. Houtteville
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Asymptomatic Patients ◽  
Familial Cerebral Cavernous Malformations

Abstract 159: Exceptional Aggressiveness of CCM3 Phenotype

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Tania J Rebeiz ◽  
Abdul Ghani Mikati ◽  
Darlene Simkhin ◽  
Cornelia Lee ◽  
Amy Akers ◽  
...  
Keyword(s):  
Spontaneous Mutation ◽  
Mutation Screening ◽  
High Sensitivity ◽  
Skin Lesions ◽  
Cerebral Cavernous Malformations ◽  
Cognitive Disability ◽  
Cavernous Malformations ◽  
Patient Advocacy Group ◽  
Sporadic Cases

Introduction: Familial forms of cerebral cavernous malformations (CCM) account for about 1/3 of cases, involving autosomal dominant inheritance at 1 of 3 gene loci. Few studies have examined any special features of the rarest cases with CCM3 (PDCD10 ) mutation at q3, constituting <15 % of probands genotyped by sequential mutation screening, and <2% of CCM cases at large. Hypothesis: We hypothesize that CCM3 cases have unique phenotypic features not recognized in the more common CCM1 and 2 families, or in sporadic cases. Methods: Twelve probands including 17 subjects with confirmed CCM3 mutations were prospectively enrolled through systematic facilitated referral by the patient advocacy group Angioma Alliance. Clinical features were catalogued, including high sensitivity susceptibility weighted imaging (SWI). Rates of overt hemorrhage were determined based on adjudicated criteria. Comparisons were made to systematic literature review of natural history data on non-CCM3 cases. Results: The first overt hemorrhage occurred most often in the 1st decade of life (mean age 5.8). Nine of 17 subjects (52%) suffered 30 overt hemorrhages, with an estimated incidence of 6.7 % /patient/year based on exposure risk since birth, and 17% /patient/year based on risk since first symptom onset. Lesion burden on SWI was exceptionally high, >100 lesions in 28%, and > 20 lesions in 72% of cases, respectively. Adjusted bleed rate was <0.5% /lesion/year. New SWI lesions formed at a rate of 2.7/patient/year in prospective follow-up, and 1.8/patient/year based on years since birth. Scoliosis was found in 47% (an association not recognized previously), skin lesions in 29.4%, and brain tumors in 29.4% of cases, respectively. Cognitive disability affected 47% of cases, mostly in association with high lesion burden. Six of 15 cases with parental screening (40%) represented a spontaneous mutation. Conclusion: CCM3 is exceptionally aggressive compared to other familial and sporadic CCM. High risks of bleeding and cognitive disability mostly reflect severe lesion burden early in life, rather than a higher risk per lesion. These results will inform the design of clinical trials, urgently needed to address this unique CCM cohort.

Description of Two Families with New Mutations in Familial Cerebral Cavernous Malformations Genes

2021 ◽  
Vol 30 (12) ◽  
pp. 106130
Author(s):  
Pablo Iruzubieta ◽  
David Campo-Caballero ◽  
Jon Equiza ◽  
Inés Albajar ◽  
Naroa Sulibarría ◽  
...  
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Familial Cerebral Cavernous Malformations ◽  
New Mutations

Mutations in KRIT1 in Familial Cerebral Cavernous Malformations

Neurosurgery ◽  
2000 ◽  
Vol 46 (5) ◽  
pp. 1272-1279 ◽  
Author(s):  
Jun Zhang ◽  
Richard E. Clatterbuck ◽  
Daniele Rigamonti ◽  
Harry C. Dietz
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Familial Cerebral Cavernous Malformations

scholarly journals Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition

Radiology ◽  
2017 ◽  
Vol 284 (2) ◽  
pp. 443-450 ◽  
Author(s):  
Corinne D. Strickland ◽  
Steven C. Eberhardt ◽  
Mary R. Bartlett ◽  
Jeffrey Nelson ◽  
Helen Kim ◽  
...  
Keyword(s):  
Ct Scans ◽  
Imaging Biomarker ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Familial Cerebral Cavernous Malformations

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.

scholarly journals Molecular genetics of familial cerebral cavernous malformations

2006 ◽  
Vol 21 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Shervin R. Dashti ◽  
Alan Hoffer ◽  
Yin C. Hu ◽  
Warren R. Selman
Keyword(s):  
Molecular Genetics ◽  
Cerebral Cavernous Malformations ◽  
Pathological Findings ◽  
Cavernous Malformations ◽  
Molecular Events ◽  
Familial Form ◽  
Hispanic Patients ◽  
Caucasian Patients ◽  
Vascular Channels ◽  
Familial Cerebral Cavernous Malformations

✓Cerebral cavernous malformations (CMs) are angiographically occult neurovascular lesions that consist of enlarged vascular channels without intervening normal parenchyma. Cavernous malformations can occur as sporadic or auto-somal-dominant inherited conditions. Approximately 50% of Hispanic patients with cerebral CMs have the familial form, compared with 10 to 20% of Caucasian patients. There is no difference in the pathological findings or presentation in the sporadic and familial forms. To date, familial CMs have been attributed to mutations at three different loci: CCM1 on 7q21.2, CCM2 on 7p15-p13, or CCM3 on 3q25.2-q27. The authors summarize the current understanding of the molecular events underlying familial CMs.

scholarly journals Spinal intramedullary cavernomas. Personal experience reffering to six cases

2014 ◽  
Vol 21 (4) ◽  
pp. 407-415 ◽  
Author(s):  
G. Iacob ◽  
Angela Olarescu
Keyword(s):  
Spinal Cord ◽  
Dorsal Surface ◽  
Neurological Status ◽  
Duration Of Symptoms ◽  
Cavernous Malformations ◽  
Excellent Outcome ◽  
Presenting Symptoms ◽  
Asymptomatic Patients ◽  
Microsurgical Techniques

Abstract Despite cavernous malformations of the CNS are pathologically similar, intramedullary cavernous malformations are very rare lesions, increasingly recognized after introduction of magnetic resonance image, generating gradual neurological decline, with severe deficits or acute loss of spinal function. We report our experience on six patients with intramedullary cavernomas defining the spectrum of presenting symptoms and signs analyzing the role of surgery as a treatment for these lesions. We present our experience with 2 cervical and 4 thoracal spinal intramedullary cavernoma from 2010 to 2014 searching history, onset of clinical manifestation, neurological status, radiological findings, operation, and clinical outcome. Among 6 patients male were 2 cases; female 4 cases; mean age was 42 years (range 25-72 years); mean duration of symptoms were 1,5 years (range 5 days and 2 years) with slowly progressive neurological decline. In two cases there was acute onset of neurological compromise. In all cases diagnosis was made on MRI and lesions were possible to be radically excised and gently extracted from the hemosiderin-stained bed inside of the spinal cord via a laminectomy and midline myelotomy with microsurgical techniques. The surgical outcome on a mean duration of follow up of 12 months were: for 4 cases - the patients neurological conditions remarkably improved 1 month later, for 2 cases no improvement were remarked. No recurrent hemorrhages were recorded. A follow-up MRI examination was made in all cases to confirm complete removal of the cavernous angioma. Spinal intramedullary cavernoma should be early recognized by MRI, can be positioned in a precarious position and generate significant neurologic deficits than cranial cavernomas. For symptomatic intramedullary cavernous malformations extended to the dorsal surface of the spinal cord, total resection with microsurgical techniques can offer good or excellent outcome, restoring neurological status and to stop chronic deterioration and acute rebleeding. To asymptomatic patients with deeper lesions which entail a higher operative risk, but also a surgically manageable cause of myelopathy a closed observation is mandatory.

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