[ITEM]
07.04.2020

Cavernous Malformation

92

Summary

Epidemiology

A cavernous malformation is an abnormal cluster of small blood vessels that. A person can have one or more cavernous malformations in their brain. Cerebral cavernous malformation A cerebral cavernous malformation is an abnormally formed blood vessel, shaped like a small mulberry, which can form in the brain or spinal column and may result in a wide range of neurological symptoms.

The overall prevalence of all CCMs has been estimated at 1/200 to 1/1,000 individuals. Familial cerebral cavernous malformation (FCCM) represents about 20% of all CCM cases with an estimated prevalence of 1/5,000 -1/10,000 and is therefore rare, contrarily to sporadic CCMs which are not. A strong founder effect has been found in Hispanic-American CCM families.

Clinical description

Close to 60% of FCCM patients are symptomatic. FCCM usually manifests between 20 to 30 years of age, but clinical manifestations can occur at any age. Symptoms include seizures (40-70%), non-specific headaches (10-30%), progressive or transient focal neurologic deficits (35-50%), and/or cerebral hemorrhages (41%). FCCM patients most often present with multiple lesions, ranging from a few millimeters to a few centimeters in size. FCCMs occur predominantly in the brain, but have also been reported in the spinal cord, retina (5% of FCCM patients) and skin.

Etiology

To date, mutations in three genes have been demonstrated to cause familial CCM; KRIT1, CCM2 and PDCD10, located on chromosome 7q21.2, 7p13, and 3q26.1 respectively, which encode proteins that, among their various functions, modulate junction formation between vascular endothelial cells.

Diagnostic methods

Cerebral magnetic resonance imaging (MRI) revealing the CCM(s) is the gold standard investigation to diagnose CCM and should include a T2 gradient echo sequence which is highly sensitive for hemosiderin. MRI shows multiple lesions in most FCCM patients in contrast with sporadic cases who harbor only one lesion. The detection of multiple CCM lesions is therefore strongly suggestive of the genetic nature of the disease. Molecular screening of FCCM genes is sometimes useful to ascertain the diagnosis in patients showing atypical MRI lesions; however, in most cases, it is used for genetic counseling.

Differential diagnosis

In cases presenting with atypical hemorrhagic MRI lesions, the differential diagnosis of FCCM includes multiple hemorrhagic metastases or hereditary cerebral hemorrhage with amyloidosis.

Cavernous malformation surgery stories

Antenatal diagnosis

Prenatal diagnosis is possible. However, in practice, very few prenatal diagnoses are requested in this disease (mostly in families where several patients have been severely affected with CCMs in the basal ganglia or spinal cord or pons).

Genetic counseling

FCCM is transmitted as an autosomal dominant trait with incomplete penetrance. Genetic counseling should be offered to the affected families informing them of the 50% risk of inheriting the mutated gene. Other important considerations in evaluating the genetic predisposition of CCMs include the number of lesions on the MRI brain scan, family history of CCM clinical characteristics, and the age of onset.

Management and treatment

Regular check-ups, generally with an MRI once a year, are recommended after the discovery of a CCM, as additional asymptomatic lesions may appear with time. These MRI check-ups can be spaced to once every 5 years in the absence of intercurrent symptoms. Treatment of seizures and headaches is symptomatic. Lesions causing severe disabling seizures and/or focal neurologic deficits and/or cerebral hemorrhages call for surgical removal of lesions whenever possible. Acetylsalicylic acid, heparin and warfarin may increase the risk of hemorrhage.

Prognosis

FCCM is an evolving condition with a strong correlation between the patient's age and the number of CCM lesions. The hemorrhagic event rate is estimated at 2-5% per lesion per year. Functional outcome is mostly conditioned by the location of CCM lesions, with brainstem and basal ganglia lesions having a worse prognosis. Available data suggest that in most patients the long-term prognosis is quite favorable with a preserved autonomy in 80% of cases.

Cerebral cavernous malformationA cerebral cavernous malformation is an abnormally formed blood vessel, shaped like a small mulberry, which can form in the brain or spinal column and may result in a wide range of neurological symptoms.Cerebral cavernous malformations (CCMs) are abnormally formed blood vessels. As opposed to other kinds of hemangiomas, CCM vessels, which have the appearance of a small mulberry, develop and create problems in the brain or spinal cord. These malformations, which can vary in size from 2 millimeters to several centimeters in diameter, may be hereditary but most often occur on their own. SymptomsCerebral cavernous malformations (CCMs) may exist without apparent symptoms. Obvious symptoms tend to occur when recurrent episodes of bleeding or blood clot formation lead either to seizures, for upper lobe CCMs, or to focal or vision issues, for CCMs in the brainstem, basal ganglia and spinal cord.Generally, signs and symptoms of CCMs may include weakness, numbness, difficulty speaking, difficulty understanding others, unsteadiness, vision changes or severe headache. Seizures also can occur, and neurological issues can progressively worsen over time with recurrent bleeding (hemorrhage).

Repeat bleeding can occur soon after an initial bleed or much later, or a repeat bleed may never occur. When to see a doctorSeek medical help immediately if you experience any symptoms of seizure, or signs and symptoms that suggest brain hemorrhage, such as:. Sudden, severe headache. Nausea.

Vomiting. Weakness or numbness on one side of the body. Difficulties in speaking or understanding speech. Loss of vision.

Double vision. Balance difficulties. CausesMost CCMs occur as a single formation, without an apparent cause and without any family history.However, roughly 20 percent of affected people have a familial (inherited) form of the disorder.

In many cases, such people can identify similarly affected family members, most often with multiple malformations. A diagnosis of the inherited form can be confirmed by genetic testing.Some CCMs can also occur following focal brain radiation therapy. Risk factorsAs mentioned above, while most CCMs occur with no clear cause, the genetic (inherited familial) form of the condition can cause multiple cavernous malformations, both initially and over time.To date, research has identified three genetic variants responsible for familial cavernous malformations, to which almost all familial cases of cavernous malformations have been traced. ComplicationsThe most concerning complications of CCMs stem from recurrent bleeding (hemorrhage), which may lead to progressive neurological damage.Hemorrhages are more likely to recur in people with prior diagnosed hemorrhages. They're also more likely to reoccur with malformations located in the brainstem. Mouchtouris N, et al.

Management of cerebral cavernous malformations: From diagnosis to treatment. The Scientific World Journal. 2015:1. Singer RJ, et al. Vascular malformations of the central nervous system. Accessed June 5, 2017.

NINDS cerebral cavernous malformation information page. National Institute of Neurological Disorders and Stroke. Accessed June 8, 2015. Moore SA, et al. Long-term natural history of incidentally discovered cavernous malformations in a single-center cohort. Journal of Neurosurgery. 2014;120:1188.

Riggin EA. Allscripts EPSi. Mayo Clinic, Rochester, Minn.

April 3, 2017. Flemming KD, et al. Management of unruptured intracranial aneurysms and cerebrovascular malformations. 2017;23:181.

Flemming KD (expert opinion). Mayo Clinic, Rochester, Minn. May 31, 2017. Tawk RG (expert opinion). Mayo Clinic, Jacksonville, Fla. May 31, 2017.

Kumar G (expert opinion). Mayo Clinic, Phoenix/Scottsdale, Ariz.

May 31, 2017. Winn H, ed. Natural history of cavernous malformations. In: Youmans and Winn Neurological Surgery.

Tetris attack for the switch free. It introduces the similar gameplay to Tetris gameplay, in which following the similar pattern, the player should remove all upcoming blocks in a row to make points. The game incorporates the elements of the battle royale genre and it pits up to 99 players against each other with an objective of completing rows with falling tetrominoes, which in turn attacks in the shape of rows to other players with an objective of knocking them out to make points. It offers 2D graphics and features two modes such as CPU Battle and more. Tetris 99 has superb features, Battle Royale mode, 2D Graphics, Classic Gameplay, and more. It lets the player to experience the multiplayer puzzle gameplay, in which 99 players must go against each other simultaneously, with the aim, similar to Battle Royale, to be the last standing player.

Philadelphia, Pa.: Elsevier; 2017. AANS/CNS Joint Cerebrovascular Section cavernous malformation information page. American Association of Neurological Surgeons. Accessed June 7, 2017. Horne MA, et al.

Clinical course of untreated cerebral cavernous malformations: A meta-analysis of individual patient data. The Lancet Neurology. 2016;15:166. Akers A, et al.

Guidelines for the clinical management of cerebral cavernous malformations: Consensus recommendations based on systematic literature review by the Angioma Alliance scientific advisory board clinical experts panel. Accessed June 7, 2017. Petr O, et al. Brainstem cavernous malformations. Journal of Neurosurgical Sciences.

2017;59:271. Brinjiki W, et al.

De novo formation of a large cavernoma associated with a congenital torcular dural arteriovenous fistula: Case report. Journal of Neurosurgical Pediatrics. 2017;19:567.

Flemming KD, et al. Seasonal variation in hemorrhage and focal neurologic deficit due to intracerebral cavernous malformations.

Journal of Clinical Neuroscience.

[/ITEM]
[/MAIN]
07.04.2020

Cavernous Malformation

73

Summary

Epidemiology

A cavernous malformation is an abnormal cluster of small blood vessels that. A person can have one or more cavernous malformations in their brain. Cerebral cavernous malformation A cerebral cavernous malformation is an abnormally formed blood vessel, shaped like a small mulberry, which can form in the brain or spinal column and may result in a wide range of neurological symptoms.

The overall prevalence of all CCMs has been estimated at 1/200 to 1/1,000 individuals. Familial cerebral cavernous malformation (FCCM) represents about 20% of all CCM cases with an estimated prevalence of 1/5,000 -1/10,000 and is therefore rare, contrarily to sporadic CCMs which are not. A strong founder effect has been found in Hispanic-American CCM families.

Clinical description

Close to 60% of FCCM patients are symptomatic. FCCM usually manifests between 20 to 30 years of age, but clinical manifestations can occur at any age. Symptoms include seizures (40-70%), non-specific headaches (10-30%), progressive or transient focal neurologic deficits (35-50%), and/or cerebral hemorrhages (41%). FCCM patients most often present with multiple lesions, ranging from a few millimeters to a few centimeters in size. FCCMs occur predominantly in the brain, but have also been reported in the spinal cord, retina (5% of FCCM patients) and skin.

Etiology

To date, mutations in three genes have been demonstrated to cause familial CCM; KRIT1, CCM2 and PDCD10, located on chromosome 7q21.2, 7p13, and 3q26.1 respectively, which encode proteins that, among their various functions, modulate junction formation between vascular endothelial cells.

Diagnostic methods

Cerebral magnetic resonance imaging (MRI) revealing the CCM(s) is the gold standard investigation to diagnose CCM and should include a T2 gradient echo sequence which is highly sensitive for hemosiderin. MRI shows multiple lesions in most FCCM patients in contrast with sporadic cases who harbor only one lesion. The detection of multiple CCM lesions is therefore strongly suggestive of the genetic nature of the disease. Molecular screening of FCCM genes is sometimes useful to ascertain the diagnosis in patients showing atypical MRI lesions; however, in most cases, it is used for genetic counseling.

Differential diagnosis

In cases presenting with atypical hemorrhagic MRI lesions, the differential diagnosis of FCCM includes multiple hemorrhagic metastases or hereditary cerebral hemorrhage with amyloidosis.

Cavernous malformation surgery stories

Antenatal diagnosis

Prenatal diagnosis is possible. However, in practice, very few prenatal diagnoses are requested in this disease (mostly in families where several patients have been severely affected with CCMs in the basal ganglia or spinal cord or pons).

Genetic counseling

FCCM is transmitted as an autosomal dominant trait with incomplete penetrance. Genetic counseling should be offered to the affected families informing them of the 50% risk of inheriting the mutated gene. Other important considerations in evaluating the genetic predisposition of CCMs include the number of lesions on the MRI brain scan, family history of CCM clinical characteristics, and the age of onset.

Management and treatment

Regular check-ups, generally with an MRI once a year, are recommended after the discovery of a CCM, as additional asymptomatic lesions may appear with time. These MRI check-ups can be spaced to once every 5 years in the absence of intercurrent symptoms. Treatment of seizures and headaches is symptomatic. Lesions causing severe disabling seizures and/or focal neurologic deficits and/or cerebral hemorrhages call for surgical removal of lesions whenever possible. Acetylsalicylic acid, heparin and warfarin may increase the risk of hemorrhage.

Prognosis

FCCM is an evolving condition with a strong correlation between the patient's age and the number of CCM lesions. The hemorrhagic event rate is estimated at 2-5% per lesion per year. Functional outcome is mostly conditioned by the location of CCM lesions, with brainstem and basal ganglia lesions having a worse prognosis. Available data suggest that in most patients the long-term prognosis is quite favorable with a preserved autonomy in 80% of cases.

Cerebral cavernous malformationA cerebral cavernous malformation is an abnormally formed blood vessel, shaped like a small mulberry, which can form in the brain or spinal column and may result in a wide range of neurological symptoms.Cerebral cavernous malformations (CCMs) are abnormally formed blood vessels. As opposed to other kinds of hemangiomas, CCM vessels, which have the appearance of a small mulberry, develop and create problems in the brain or spinal cord. These malformations, which can vary in size from 2 millimeters to several centimeters in diameter, may be hereditary but most often occur on their own. SymptomsCerebral cavernous malformations (CCMs) may exist without apparent symptoms. Obvious symptoms tend to occur when recurrent episodes of bleeding or blood clot formation lead either to seizures, for upper lobe CCMs, or to focal or vision issues, for CCMs in the brainstem, basal ganglia and spinal cord.Generally, signs and symptoms of CCMs may include weakness, numbness, difficulty speaking, difficulty understanding others, unsteadiness, vision changes or severe headache. Seizures also can occur, and neurological issues can progressively worsen over time with recurrent bleeding (hemorrhage).

Repeat bleeding can occur soon after an initial bleed or much later, or a repeat bleed may never occur. When to see a doctorSeek medical help immediately if you experience any symptoms of seizure, or signs and symptoms that suggest brain hemorrhage, such as:. Sudden, severe headache. Nausea.

Vomiting. Weakness or numbness on one side of the body. Difficulties in speaking or understanding speech. Loss of vision.

Double vision. Balance difficulties. CausesMost CCMs occur as a single formation, without an apparent cause and without any family history.However, roughly 20 percent of affected people have a familial (inherited) form of the disorder.

In many cases, such people can identify similarly affected family members, most often with multiple malformations. A diagnosis of the inherited form can be confirmed by genetic testing.Some CCMs can also occur following focal brain radiation therapy. Risk factorsAs mentioned above, while most CCMs occur with no clear cause, the genetic (inherited familial) form of the condition can cause multiple cavernous malformations, both initially and over time.To date, research has identified three genetic variants responsible for familial cavernous malformations, to which almost all familial cases of cavernous malformations have been traced. ComplicationsThe most concerning complications of CCMs stem from recurrent bleeding (hemorrhage), which may lead to progressive neurological damage.Hemorrhages are more likely to recur in people with prior diagnosed hemorrhages. They're also more likely to reoccur with malformations located in the brainstem. Mouchtouris N, et al.

Management of cerebral cavernous malformations: From diagnosis to treatment. The Scientific World Journal. 2015:1. Singer RJ, et al. Vascular malformations of the central nervous system. Accessed June 5, 2017.

NINDS cerebral cavernous malformation information page. National Institute of Neurological Disorders and Stroke. Accessed June 8, 2015. Moore SA, et al. Long-term natural history of incidentally discovered cavernous malformations in a single-center cohort. Journal of Neurosurgery. 2014;120:1188.

Riggin EA. Allscripts EPSi. Mayo Clinic, Rochester, Minn.

April 3, 2017. Flemming KD, et al. Management of unruptured intracranial aneurysms and cerebrovascular malformations. 2017;23:181.

Flemming KD (expert opinion). Mayo Clinic, Rochester, Minn. May 31, 2017. Tawk RG (expert opinion). Mayo Clinic, Jacksonville, Fla. May 31, 2017.

Kumar G (expert opinion). Mayo Clinic, Phoenix/Scottsdale, Ariz.

May 31, 2017. Winn H, ed. Natural history of cavernous malformations. In: Youmans and Winn Neurological Surgery.

Tetris attack for the switch free. It introduces the similar gameplay to Tetris gameplay, in which following the similar pattern, the player should remove all upcoming blocks in a row to make points. The game incorporates the elements of the battle royale genre and it pits up to 99 players against each other with an objective of completing rows with falling tetrominoes, which in turn attacks in the shape of rows to other players with an objective of knocking them out to make points. It offers 2D graphics and features two modes such as CPU Battle and more. Tetris 99 has superb features, Battle Royale mode, 2D Graphics, Classic Gameplay, and more. It lets the player to experience the multiplayer puzzle gameplay, in which 99 players must go against each other simultaneously, with the aim, similar to Battle Royale, to be the last standing player.

Philadelphia, Pa.: Elsevier; 2017. AANS/CNS Joint Cerebrovascular Section cavernous malformation information page. American Association of Neurological Surgeons. Accessed June 7, 2017. Horne MA, et al.

Clinical course of untreated cerebral cavernous malformations: A meta-analysis of individual patient data. The Lancet Neurology. 2016;15:166. Akers A, et al.

Guidelines for the clinical management of cerebral cavernous malformations: Consensus recommendations based on systematic literature review by the Angioma Alliance scientific advisory board clinical experts panel. Accessed June 7, 2017. Petr O, et al. Brainstem cavernous malformations. Journal of Neurosurgical Sciences.

2017;59:271. Brinjiki W, et al.

De novo formation of a large cavernoma associated with a congenital torcular dural arteriovenous fistula: Case report. Journal of Neurosurgical Pediatrics. 2017;19:567.

Flemming KD, et al. Seasonal variation in hemorrhage and focal neurologic deficit due to intracerebral cavernous malformations.

Journal of Clinical Neuroscience.