Arteriovenous malformation
PKGhatak,MD
In 2011 Mike Patterson, a prominent Philadelphia Eagles football player, had a seizure on the playing field. Later in the day, it was determined that Mike's seizure was due to an arteriovenous malformation in the brain. In the succeeding months, more known cases of arteriovenous malformation (AVM) in celebrities became known. It is estimated that 1 in every 100,000 world population has AVM, however, most of them did not have any symptoms.
AVM develops when the artery makes a direct path to the veins without first connecting with capillaries. AVM may arise in any place in the body, however, when present in the brain or spinal cord they tend to be symptomatic. When AVM in the brain enlarges it produces pulsating pain, nausea, vomiting, and various neurological symptoms depending on the location and seizures. When AVM ruptures it becomes a catastrophic event.
AVM is an inherited condition but also occurs due to somatic gene mutations, and occasionally following injuries and stab wounds. In some cases, AVM develops from cavitary pulmonary tuberculosis, schistosomiasis, and juvenile hepatic cirrhosis. It is a difficult task to determine the mode of inheritance in every case of AVM. There are about 600 mutations of genes associated with AVM. The well known Osler- Rendu- Weber syndrome or hereditary hemorrhagic telangiectasia (HHT) is due to autosomal dominant inheritance. The mutated gene is two No1. Endigin gene mutation is present on chromosomes 9, and No 2. Activin receptor kinase gene mutation is present on chromosome 12. Just one copy of one of the two mutated genes will manifest as HHT. The MADH4 gene mutation is associated with colon polyps and AVM. These genes are under the control of the RASA1 gene. In normal circumstances, the RASA1 gene transcribes a protein kinase controlling capillary formation. In HHT blood vessel developments are defective at several levels due to abnormal cytokine function.
At birth, most of the AVMs are small and may not be visible but as the child grows, the AVM enlarges and in adolescence, the enlargement accelerates. AVMs on the face, neck, and chest wall are often associated with visceral AVM. AVMs tend to grow for a period and then regress spontaneously, in some others continue to slow growth.
Besides AVM, congenital abnormalities of veins, capillaries and lymphatics are known. But the incidence of these abnormalities is less frequent.
Pulmonary AVM.
The AVM of the lung is usually small and remains asymptomatic. Multiple or larger AVMs are detected in chest x-rays. In rare instances, a large AVM occupies an entire lobe or two lobes of the lungs called diffuse AVM. AVM of the lung is seen in 40% of hereditary hemorrhagic telangiectasia.
Pulmonary AVM usually produces recurrent hemoptysis, pneumothorax, hemothorax, recurrent pneumonia, septicemia and TB, and other infections. Large and diffuse AVM produces low oxygen saturation of the arterial blood (PaO2). Low PaO2 is due to pulmonary arterial blood, instead of going to the alveoli, drains directly into the pulmonary veins. A Right to Left shunt develops. Hypoxic symptoms arising from the brain, liver and kidneys begin early; and congestive heart failure is a late development.
Cerebro-spinal AVM.
AVM of the brain is present in 30% of HHT and about 1 % of AVM is located in the spinal cord. Most of these AVMs are symptomatic. Initially, the symptoms are mild and nonspecific - headache, seizures, visual or speech problems, balance and ambulation abnormalities. Any increase in the size of the AVM either due to growth or infection or bleeding/ clot formation produces a symptom depending on the location of the AVM. Visual field loss, diplopia, cranial nerve palsy, weakness of limbs or incoordination are usual symptoms. Pulsating noise in the head is a distinct symptom due to the rapid flow of blood from an artery to a vein. Infections and rupture of AVM are real possibilities. Rupture of AVM may be the first presenting symptom and such incidences are as high as 50%. Intense headaches and rapid onset of coma usually follow. If treatment is delayed the outcome is bad. Infected emboli from the lung result in brain abscesses. Meningoencephalitis, high pressure hydrocephalus, seizures, cranial nerve palsy and hemiparesis are complications from the infection.
Renal and genitourinary AVM.
Hematuria, repeated UTI and vaginal bleeding and uterine infection in women are seen but less frequently.
Hepatic AVM.
Most of the AVMs are small and maybe multiple and remain silent. In HHT the incidence of hepatic AVMs is 40%. The chances of infection of AVM in the liver are high. Pain in the upper right quadrant of the abdomen is the presenting symptom. Infection of the liver, cholangiohepatitis, hepatic insufficiency, and intra-abdominal bleeding occur. Portal hypertension, esophageal varies and GI bleeding is seen.
Hereditary Hemorrhagic Telangiectasia.
HHT is an autosomal dominant hereditary disease, in North America, the incidence of HHT is 1 in 10,000 population. Mucocutaneous telangiectasia of lips is a distinct feature and is present in 95% of HHT. The bluish dilated venules of the lips and floor of the mouth and tongue are present at ages 10 to 20s. Telangiectasia of the fingertips and chest wall develops in ages 30 to 40s. Nose bleeding in HHT is a daily occurrence and leads to iron deficiency anemia and occasionally requires a blood transfusion.
Another feature of HHT is bleeding AVM from the stomach and small intestine. The GI bleeding may be massive. Hemoptysis and neurological symptoms develop from AVM of the lungs and brain respectively.
One word of caution – bronchoscopy or endoscopy procedures must be conducted with extreme care. Biopsy of tissue is strictly prohibited, once bleeding starts the control of bleeding is nearly impossible except removal of the organ by immediate surgery.
Cutaneous AVM.
The port-wine stain of the face chest wall and other areas of the body is due to skin capillary AVM, often cutaneous AVM is associated with visceral AVM.
Diagnosis and Treatment.
Recurrent hemoptysis, GI, or genitourinary bleeding, when accompanied by cutaneous telangiectasia diagnosis, is not difficult. Most large sized pulmonary AVMs are symptomatic. Bluish discoloration of lips and fingers, clubbing of fingers and a distinct humming noise on chest auscultation, presence of right heart enlargement and congestive heart failure, features of neurological symptoms when present together the clinical diagnosis is almost certain.
Imaging is very helpful. Contrast enhanced CT is very specific. MRI, Angio-CT and the new generation of Doppler Ultrasound scans have replaced most other diagnostic tools of the earlier days - like Bubble tests and Angiograms. In the bubble test, several microbubbles are injected on the venous side and microbubbles are detected by ultrasound scans of the arteries.
Controlling bleeding where possible is attempted first, but in most cases immediate embolization of the artery is necessary. Other therapeutic options are - sclerotherapy or laser coagulation. If non-surgical treatment to control bleeding fails then surgery is the only option that remains. In cases of distressing nose bleeds various forms of plastic surgery procedures are attempted to patch over the location of telangiectasia.
In HHT the family members are strongly encouraged to undergo genetic testing and counseling.
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