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Brain abscess as a sign of a hereditary disease

Torry Grantham Cobb, MPH, MHS, PA-C

Torry Cobb practices as a physician assistant in the Department of Neurological Surgery, Marshfield Clinic, Marshfield, Wisconsin. She has indicated no relationships to disclose relating to the content of this article.

CASE

A 38-year-old white male presented to the emergency department (ED) with a 3-day history of persistent headache. The headache was located in the left temporoparietal area and had improved temporarily with the use of acetaminophen (Tylenol) at home. The patient denied fever, nausea, vomiting, or visual changes but admitted to some word-finding difficulties. In the ED, vital signs and physical examination findings were considered normal, although the patient’s speech was not formally assessed.

The medical history was significant for Osler-Weber-Rendu disease also known as hereditary hemorrhagic telangiectasia (HHT). The patient had received this diagnosis in 1989, after his mother had undergone a brain biopsy for a lesion that was determined to be a brain abscess. He and his mother had pulmonary arteriovenous malformations (AVMs), identified on angiography, which were subsequently treated by coiling. Previously, the patient’s clinical manifestations of HHT had been limited to occasional nosebleeds.

While in the ED, the patient underwent CT of the head, and a 2.922.7-cm heterogeneous mass was noted in the left frontal region (see Figure 1). Treatment with dexamethasone was started, and the patient was referred to neurosurgery and underwent MRI of the brain (see Figure 2).

The patient was examined by the neurosurgery service and found to be a well-appearing young gentleman. His headaches had improved minimally. He continued to complain of mild word-finding difficulties, which were confirmed with formal examination. No other focal neurologic deficits were noted. At that time, surgical intervention was recommended for both diagnostic and treatment purposes. The differential diagnosis included neoplasm and abscess.

In the OR, the patient underwent a left frontal craniotomy. Intraoperatively, a discoloration was noted over what was likely the left middle frontal gyrus. Using the operating microscope, the surgeon made a small, less than 1-cm corticectomy in the area of abnormality in the frontal lobe. As the corticectomy was deepened 2 to 3 mm, there was immediate egress of yellowish purulent material; 8 to 12 cc was aspirated into a syringe and sent for multiple cultures and Gram’s stain. The cyst wall was noted to be mature and was dissected from the surrounding white matter. The pathology from the frozen sections confirmed the lesion to be an abscess with obvious microbes (gram-positive cocci and rare gram-negative bacilli) present.

An infectious disease consult was obtained postoperatively. The patient was started on ceftriaxone (Rocephin), 2 g IV every 12 hours, and metronidazole (Flagyl IV, Metro IV), 500 mg IV every 8 hours. He did well postoperatively. His word-finding difficulties improved, and his headaches resolved. The dexamethasone was tapered and ultimately discontinued. A repeat chest film revealed the pulmonary AVM coil to be in place. No new lesions were identified. Cultures grew Fusobacterium nucleatum sensitive to metronidazole and Actinomyces odontolyticus and Peptostreptococcus micros sensitive to ceftriaxone. The patient was discharged on postoperative day 4 and continued to receive IV ceftriaxone and metronidazole at home.

Three weeks after surgery, the patient was switched from IV to oral metronidazole. At 4 weeks postoperatively, the IV ceftriaxone and the oral metronidazole were discontinued, and the patient was started on oral amoxicillin (Amoxil), 1,000 mg 3 times a day. He continued to take this medication for 4½ months. A repeat head CT obtained 6 weeks after surgery revealed a small area of encephalomalacia in the left frontal lobe (see Figure 3). Otherwise, the vasogenic edema that was present preoperatively had completely resolved. Clinically, the patient was doing well, and his speech difficulties had resolved.

DISCUSSION

Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder associated with the triad of recurrent epistaxis, telangiectasias (mucocutaneous or visceral), and a positive family history of HHT. Morbidity and mortality result from multi-organ AVMs and their associated hemorrhages. The disease has a wide variety of manifestations. Patients may be asymptomatic at presentation or have multiple organ involvement, and they can present at any age. The majority of the morbidity and mortality is a consequence of untreated pulmonary and other AVMs and their associated hemorrhages. Thus, treatment is aimed at identifying AVMs and preventing and treating bleeding.

The diagnosis of HHT is based on the Curaçao criteria (see Table 1). The diagnosis can be made on the basis of clinical findings, but a skin biopsy can confirm the condition. Findings are localized in the dermal upper-horizontal plexus. The classic features are dilated capillaries and new vessel formation. In the dermis, the walls of dilated vessels may be thickened.

Epidemiology In the United States, the prevalence of HHT is 1 to 2 cases per 100,000 population.^1-3 Worldwide, the prevalence is the same, but higher incidences have been noted on the Danish island of Fyn, the Dutch Antilles, and parts of France.¹ The incidence of brain abscess associated with HHT is 1.3 per 100,000 cases diagnosed.⁴ The disease affects all races and males and females equally. HHT can manifest in childhood as a tendency to bleed but is much more common in puberty and adulthood. It often becomes clinically apparent by the second or third decade of life.

Pathophysiology Two genes may be implicated in HHT: the endoglin gene (ENG) and the activin receptorlike kinase type I gene (ALK-1).⁵ Abnormal vessel repair may be caused by defects in the proteins coded by ENG or ALK-1. Various mutations of these genes, including missense, nonsense, frameshift, and deletion mutations, have been identified in patients with HHT. Although the mechanism is not well understood, the bleeding tendency is felt to be due to vessel wall weakness.

Clinical manifestations The typical telangiectasia in HHT is smaller than 5 mm and can be found directly beneath the skin or mucosal surface. These vessels can be found in the brain, liver, and spleen, as well as in the GI, respiratory, and urinary tracts.

Skin Typical skin lesions are smaller than 5 mm and range in color from bright red to purple. They may appear as macular, papular, or punctate areas and generally partially blanch with pressure. Linear or spiderlike lesions are rare. The face, lips, mouth, nares, tongue, ears, hands, chest, and feet are most often affected. These skin lesions are often more of a cosmetic concern than a sign of hemorrhage.

Nose The most common symptom in patients with HHT is recurrent epistaxis. This generally manifests at a young age, usually before 10 years. Bleeding may occur spontaneously and be severe enough to warrant blood transfusion and/or iron supplementation. Many patients experience an increased tendency to bleed with advancing age.

CNS Primary lesions such as cerebral and spinal AVMs, cavernous angiomas, and aneurysms manifest as hemorrhagic stroke, subarachnoid hemorrhage, migraine, seizures, and paraparesis. These account for approximately one-third of CNS problems. The estimated incidence of CNS AVMs in patients with HHT is 5% to 10%.⁶ Stereotactic radiosurgery is now generally a preferred method of treating brain AVMs.

Other CNS manifestions are the result of pulmonary AVMs. Neurologic complications of pulmonary AVMs include ischemic stroke and brain abscess (the results of bacterial seeding).² These have often been noted as the initial manifestation of HHT.^7-11 Pulmonary AVMs also contribute to an increased incidence of brain abscesses. Up to 5% of patients with pulmonary AVMs develop a brain abscess.^3,12 Of patients who have pulmonary AVMs, 2% per year have a stroke and an estimated 1% per year develop a brain abscess.¹³ Strokes and brain abscesses are the leading causes of mortality in HHT patients.

Other organ systems Pulmonary AVMs are perhaps the most important manifestation of HHT because of their CNS effects. Pulmonary AVMs are also treatable. Patients with small AVMs with shunting of less than 25% of blood flow may be asymptomatic at rest but often have dyspnea on exertion and are easily fatigued.³ Patients with larger or multiple AVMs will often have clubbing, cyanosis, and polycythemia.

Approximately 10% to 40% of patients with HHT experience GI bleeding.^1,3 As with epistaxis, the tendency to bleed increases with age. GI bleeding is more commonly seen in the fifth or sixth decade of life and occurs as the result of both telangiectasias and AVMs. Colonoscopy shows GI telangiectasias surrounded by an anemic halo.

A diffuse telangiectatic process in the liver has been noted in 8% to 31% of patients with HHT.¹⁴ Although some patients may be asymptomatic, others may have high-output heart failure, hepatomegaly, encephalopathy, portal hypertension, jaundice, biliary pain, or abdominal mesenteric pain. Patients with clinically significant liver lesions most often present with hyperdynamic circulation (cardiac indexes of 4.6-6.8 L/min/m²). This phenomenon is observed even without symptoms of heart failure and is due to shunting from the hepatic artery to hepatic vein, the portal vein to hepatic vein, or both. Shunting from the hepatic artery to portal vein causes arterialization of the portal system with nodular transformation of parenchyma without fibrous septa, a condition termed pseudocirrhosis.

Diagnosis and treatment Laboratory studies should evaluate the blood for iron deficiency anemia and thrombocytopenia. Patients can also be polycythemic as a result of chronic hypoxemia. Liver function tests may reveal elevated enzyme levels. Urine and stool should be evaluated for the presence of blood. Imaging studies such as chest radiography, angiography, CT, and MRI may be needed to evaluate for AVMs.

Most patients with HHT have a favorable prognosis, depending on the degree of systemic involvement. Generally, patients with pulmonary, hepatic, and CNS involvement have a worse prognosis. Approximately 10% of patients die from disease complications. Despite the variety of clinical presentations and the potential for devastating complications, patients with HHT are generally considered to have normal life spans.

Long-term follow-up care is necessary because additional AVMs tend to develop with advancing age. Patients with known HHT should undergo annual screening for lung and brain AVMs, before symptoms develop. A pregnant woman should have a pulmonary evaluation as soon as pregnancy is recognized.

Other manifestations of HHT can be treated symptomatically. A yearly physical evaluation by a provider familiar with HHT and its symptoms is recommended, as is an annual check of hemoglobin/hematocrit. Antibiotic prophylaxis is advised before dental or surgical procedures, including dental cleanings for all patients with pulmonary AVMs, even if previously embolized.

Finally, patients should be referred for genetic counseling, because HHT is an autosomal dominant disorder in which the homozygous form is considered lethal.¹⁵ The Hereditary Hemorrhagic Telangiectasia Foundation International (www.hht.org) hosts annual conferences, educates families and practitioners, and provides research funding for HHT. Numerous support groups for individuals and families are available as well. JAAPA

Steve Wilson, PA-C, department editor

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