Cavernous hemangioma

People with this condition in the brain may or may not experience symptoms. Some complications of the condition are life-threatening or cause major disruptions to normal functioning. Dangerous seizures due to compression of the brain, bleeding inside the brain tissue, vision problems, difficulty with speaking or using words, memory loss, ataxia, or hydrocephalus can occur. Less serious symptoms may include headaches and weakness or numbness in the arms or legs, though these symptoms alone do not indicate a person has the condition. In the eye, it may cause disruption or damage to the extraocular muscles and optic nerve which may manifest as double vision, progressive proptosis, decreased visual acuity, or other vision changes. It can lead to partial or complete blindness. When the condition occurs in the liver it usually does not cause symptoms, but some may experience pain in the upper right abdomen, a feeling of fullness after eating only a small amount of food, decreased appetite, nausea, or vomiting. ==Presentation==

Cavernous hemangiomas can arise nearly anywhere in the body where there are blood vessels. They are sometimes described as resembling raspberries because of the appearance of bubble-like caverns. Unlike capillary hemangiomas, cavernous ones can be life-threatening and do not regress. Causes Most cases of cavernomas are thought to be congenital; however they can develop over the course of a lifetime. While there is no definitive cause, research suggests that genetic mutations cause the condition. Congenital hemangiomas that appear on the skin are known as either vascular or red birthmarks. Familial cerebral cavernous malformations are known to occur. The mutations may be inherited in an autosomal dominant fashion or occur sporadically. Overall, familial disease is thought to be responsible for one-third to one-half of cases. In the US, approximately 50% of Hispanic patients with cerebral cavernous malformations have a familial form. In contrast, the familial form of the condition accounts for only 10 to 20% of cases in Caucasians. The reason for this difference is not presently known. Several genes – K-Rev interaction trapped 1 (ССМ1), malcavernin (CCM2) and programmed cell death protein 10 (ССМ3) – have been identified as having mutations thought to be related to these lesions. These genes are located at 7q21.2 (chromosome 7 long arm), 7p13 (chromosome 7 short arm) and 3q25.2-q27 (chromosome 3 long arm) respectively. These lesions are further discussed in the Online Mendelian Inheritance in Man site – the reference numbers are OMIM 116860, OMIM 603284 and OMIM 603285 respectively. ==Variations==

Cerebral cavernomas Cavernous hemangiomas located in the brain or spinal cord are referred to as cerebral cavernomas or more usually as cerebral cavernous malformations (CCMs), Usually one malformation exists, but multiple lesions can occur in the left or right lobe of the liver in 40% of patients. Their sizes can range from a few millimeters to 20 centimetres. Those over 5 cm are often referred to as giant hemangiomas. This neoplasm is usually located within the muscle cone, which is lateral to the optic nerve. It is not usually treated unless the patient is symptomatic. Visual impairment happens when the optic nerve is compressed or the extraocular muscles are surrounded. ==Mechanism==

There are several known causes for cavernous hemangiomas, but some cases are still unknown. Radiation treatment used for other medical conditions has been suggested to cause cavernous malformation in some patients. Furthermore, it is also believed that a "second hit mutation" is necessary for the onset of the disease. This means that having a mutation in one of the two genes present on a chromosome is not enough to cause the cavernous malformation, but mutation of both alleles would cause the malformation. Additionally, research on hemangiomas in general has shown that loss of heterozygosity is common in tissue where hemangioma develops. This would confirm that more than a single allele mutation is needed for the abnormal cell proliferation. KRIT1 has been shown to act as a transcription factor in the development of arterial blood vessels in mice. CCM2 has overlapping structure with CCM1 (KRIT1) and acts as a scaffolding protein when expressed. Both genes are involved with MAP3K3 and thus appear to be a part of the same pathway. pathways CCM2 has been shown to cause embryonic death in mice. Lastly, the CCM3 gene has been shown to have similar expression to CCM1 and CCM2, suggesting a link in its functionality. no experiments have determined its exact function. The lack of function of these genes in control of a proliferative signaling pathway would result in uncontrolled proliferation and the development of a tumor. In 2018, it was theorized that proliferation of endothelial cells with dysfunctional tight junctions, that are under increased endothelial stress from elevated venous pressure provides the pathophysiological basis for cavernous hemangioma development. In 2017 a team demonstrated that negative regulation of MAP3K3 (MEKK3), KLF2, and KLF4 are implicated in the pathogenesis of CCM. Additionally, they identified endothelial Toll-like receptor 4 (TLR4) and it's relationship with the gut microbiome as a driving factor in CCM formation. ==Diagnosis==

Gradient-echo T2WI magnetic resonance imaging (MRI) is the most sensitive method for diagnosing cavernous hemangiomas. MRI is such a powerful tool for diagnosis that it has led to an increase in diagnosis of cavernous hemangiomas since the technology's advent in the 1980s. The radiographic appearance is most commonly described as "popcorn" or "mulberry"-shaped. Computed tomography (CT) scanning is not a sensitive or specific method for diagnosing cavernous hemangiomas. Angiography is typically not necessary, unless it is required to rule out other diagnoses. Additionally, biopsies can be obtained from tumor tissue for examination under a microscope. It is essential to differentially diagnose cavernous hemangioma because treatments for these lesions are less aggressive than that of cancerous tumors, such as angiosarcoma. However, since MRI appearance is practically pathognomonic, biopsy is rarely needed for verification. ==Treatment==

Asymptomatic lesions may not require treatment but may need to be monitored for any change in size. A change in size of lesions in the nose, lips, or eyelids can be treated with steroid drugs to slow progress. Steroids can be taken orally or injected directly into the tumor. Applying pressure to the tumor can also be used to minimize swelling at the site of the hemangioma. A procedure that uses small particles to close off the blood supply, known as sclerotherapy, promotes tumor shrinkage and pain reduction; hovever it is possible for the tumor to regrow its blood supply after this procedure. If the lesion caused by the cavernous hemangioma is destroying healthy tissue around it, or if the patient is experiencing major symptoms, surgery can be used to remove the cavernoma piecemeal. The treatment approach depends on the site, size and symptoms present, as well as the history of hemorrhage from the lesion. Not enough data has been collected on life expentancy of patients with this malformation to provide a representative statistical analysis. ==Epidemiology==

The true incidence of cavernous hemangiomas is difficult to estimate because they are frequently misdiagnosed as other venous malformations. Cavernous hemangiomas of the brain and spinal cord (cerebral cavernous hemangiomas (malformations) (CCM)), can appear at all ages, but usually occur in the third to fourth decade of the life of a person of either sex; CCM is present in 0.5% of the population. However, approximately 40% of those with malformations have symptoms. Asymptomatic affected individuals have usually developed the malformation sporadically, while symptomatic individuals have usually inherited the genetic mutation. Liver hemangiomas usually occur between the ages of 30 and 50 and more commonly in women. Cases of infantile liver cavernomas are extremely rare. Cavernous hemangioma of the eye is more prevalent in women than men, usually between the ages of 20 and 40. • Alberto Contador (), Spanish retired cyclist • Florence Griffith Joyner (1959–1998), American track and field runner • Louise Krug (b. ), American author of the memoir Louise: Amended about her diagnosis • Rafael Lovato Jr. (b. 1983), Brazilian jiu-jitsu fighter and former MMA fighter • Frederick Ma (b. 1952), Hong Kong politician and businessman • Federico Melchiorri (b. 1987), Italian footballer • Marvin Morgan (1983–2021), English footballer • Bujar Nishani (1966–2022), former President of Albania • Jeff Tarpinian (b. 1987), American retired football linebacker • Ryan Westmoreland (b. 1990), American retired baseball player ==Research==

In the treatment of a brain cavernous hemangioma, neurosurgery is usually the treatment chosen. Research needs to be conducted on the efficacy of treatment with stereotactic radiation therapy, especially on the long-term. However, radiotherapy is still being studied as a form of treatment if neurosurgery is too dangerous due to the location of the cavernoma. Genetic researchers are still working on determining the cause of the illness and the mechanism behind blood vessel formation. Clinical trials are being conducted to better assess when it is appropriate to treat a patient with this malformation and with what treatment method. An existing registry known as The International Cavernous Angioma Patient Registry collects information from patients diagnosed with cavernoma in order to facilitate discovery of non-invasive treatments. == References ==