Cavernous malformations.
Article Type: Report
Subject: Blood vessels (Abnormalities)
Neurovascular diseases (Diagnosis)
Neurovascular diseases (Care and treatment)
Author: Ryan, Denita
Pub Date: 10/01/2010
Publication: Name: Journal of Neuroscience Nursing Publisher: American Association of Neuroscience Nurses Audience: Professional Format: Magazine/Journal Subject: Health care industry Copyright: COPYRIGHT 2010 American Association of Neuroscience Nurses ISSN: 0888-0395
Issue: Date: Oct, 2010 Source Volume: 42 Source Issue: 5
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 238912121
Full Text: ABSTRACT

Cavernous malformations (CMs) are a subset of neurovascular malformations, which include arteriovenous malformations (AVMs), venous malformations, and capillary telangiectasias. CMs are referred to by many names, which may contribute to their being mistaken for malignant entities such as angiomas or hemangiomas. They are not, however, neoplastic; they are true vascular malformations with their own natural history and treatment. This article describes CMs and their clinical manifestations, methods of diagnosis, and types of treatment. CMs exist in both sporadic and familial forms. Nurses caring for patients with CMs should be aware of the specific characteristics of CMs that differentiate them from other neurovascular lesions.

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Cavernous malformations (CMs) are a subset of neurovascular malformations, which includes arteriovenous malformations (AVMs), venous malformations, and capillary telangiectasias. CMs are often misdiagnosed as other types of lesions, a problem complicated by confusing nomenclature in the literature. CMs have been referred to by many names, such as cavernous angiomas, cavernous hemangiomas, capillary hemangiomas, or cavernomas. They have also been mistaken for malignant entities such as angiomas or hemangiomas (Table 1). CMs, however, are not neoplastic; they are tree vascular malformations with their own natural history and treatment paradigm.

With the advent of magnetic resonance imaging (MRI), CMs, once considered to be tumors or other types of vascular malformations, can now be diagnosed appropriately. CMs are dynamic lesions that can occur anywhere in the central nervous system (CNS); hence, they are appropriately termed neurovascular rather than cerebrovascular malformations. Caring for patients with CMs requires understanding the epidemiology and natural history of the disease. This article therefore defines CMs, describes the unique features that differentiate them from other neurovascular lesions, and discusses their natural history and related treatment options in terms of their implications for nursing care.

Definition

On gross inspection, CMs are well circumscribed, dark red to purple, multilobulated masses described as having a "mulberry-like" appearance (Figure 1). They may be as small as several millimeters or as large as several centimeters. They are clusters of abnormal, sinusoidal, contiguous, vascular channels of various sizes separated by dense fibrous tissue with little or no intervening brain parenchyma. The vascular channels may contain various amounts of blood in different stages of thrombus and degradation. CMs are always surrounded by hemosiderin, an insoluble substance that contains iron salts and indicates the presence of hemorrhage. This hemosiderin ring has been attributed to multiple episodes of hemorrhage over time. CMs have no neoplastic features.

Epidemiology

CMs account for approximately 1% of all intracranial mass lesions and approximately 15% of all neurovascular lesions. They are found at autopsy or on routine imaging studies in about 0.4% of the population (Metellus, Kharkan, Kapoor, Lin, & Rigamonte, 2008).

CMs can occur in any age group but are least common in the elderly. Approximately 25% of all CMs occur in children (Hsu, Rigamonti, & Huhn, 1993). However, the typical age at presentation ranges between 20 and 40 years. There is no gender predilection.

There are two types of CMs: sporadic and familial. Most CMs occur as solitary lesions, but a third of all patients with sporadic CMs can have multiple lesions. Of patients with the familial form of CMs, 73% have multiple lesions (Maraire & Awad, 1995). CMs have been reported to occur in conjunction with other intracranial vascular lesions. Many CMs are associated with an enlarged vein known as a venous anomaly.

Genetics and the Familial Form

The familial form of CMs are congenital lesions. The familial form of CMs is most prevalent in Mexican American families (Flemming, Goodman, & Meyer, 2003), where this form was first recognized (Rigamonti et al., 1988). Familial CMs are transmitted in an autosomally dominant fashion with variable penetrance (40%-60%). The hallmark of familial CMs is a strong family history of seizures and the presence of multiple lesions. At least three genetic foci have been identified: CCM1 on 7q, CCm2 on 7p, and CCM3 on 3q (Craig et al., 1998; Denier et al., 2004; Dubovsky et al., 1995; Dupre et al., 2003). Verlaan et al. (2004) found that 29% of individuals with multiple CMs had a CCM1 mutation, whereas those with single lesions did not. Mutations of the gene CCM1, which is located on chromosome 7q21.2, account for a large percentage of patients with the familial form of the disease. This mutation is present in most Hispanics with the familial form and in almost 40% of all non-Hispanics with the familial form (Verlaan et al., 2004). The disease gene responsible for CCM1 encodes KRIT1 (Denier et al., 2004). As documented by neuroimaging, half of the patients with multiple CMs have family members who also have CMs (Zabramski et al., 1994a).

Clinical Manifestations

The signs and symptoms of clinical presentation depend on the location of the lesion. CMs occur in all areas of the central nervous system, proportional to the volume of tissue in the major regions. Approximately 80% of intracranial CMs are located supratentorially. Infratentorial CMs, distributed between the brainstem and the cerebellum, account for approximately another 15%. Brainstem CMs represent 9% to 35% of all CMs (Nakaji, 2005). Approximately 5% of CMs involve the spinal cord. In a study performed at St. Joseph's Hospital in Phoenix, Arizona, almost half of the patients with intramedullary spinal cord malformations had multiple lesions (Vishteh, Zabramski, & Spetzler, 1999). Of these spinal cord lesions, most were cervical (75%). The remaining lesions (25%) were located in the thoracic region. Very rarely, CMs involve the cranial nerves, particularly the optic, oculomotor, facial, and vestibulocochlear nerves (Deshmukh, Albuquerque, Zabramski, & Spetzler, 2003).

Most CMs are asymptomatic (Feiz-Erfan, Zabramski, Lanzino, & Porter, 2002). Symptomatic CMs, however, can manifest with seizures, headaches, focal neurological deficits, or all three. Moriarity et al. (1999) reported that approximately 65% of patients with CMs complained of headache, whereas 49% of patients had a history of seizures. Symptoms can result directly from hemorrhage, but hemorrhage can also be asymptomatic.

The reported rate of hemorrhage associated with supratentorial CMs varies between 2% and 4% per lesion per year. Rehemorrhage rates are approximately 5% per lesion per year. The hemorrhage rates associated with lesions deep in the brain or in the brain stem may be as much as 30 times higher (Porter, Willinsky, Harper, & Wallace, 1997). Overall, the risk of hemorrhage associated with brainstem CMs is 3.8%, and their rate of rebleeding is 34.7% (Ferroli et al., 2005). CMs appear to be grow more actively in younger children than that in older patients, accounting for more presenting symptoms than that in adults. Pediatric patients may have a higher incidence of hemorrhage than adults (Bergeson, Rekate, & Tack, 1992).

Seizures, the most common manifestation of supratentorial CMs, account for 40% to 80% of presenting symptoms (Del Curling, Kelly, Elster, & Craven, 1991; Rigamonti et al., 1988; Robinson, Awad, & Little, 1991; Zabramski et al., 1994b). The mechanism underlying the seizures is unknown but has been attributed to the deposition of iron in the hemosiderin. The iron component of hemosiderin is known to be epileptogenic. Studies have shown that between 34% and 81% of patients with CMs have seizures (Smith, Javedan, Zabramski, Blum, & Spetzler, 2002). Supratentorial CMs rarely become symptomatic with focal neurological deficits.

[FIGURE 1 OMITTED]

CMs involving the brain stem, however, most often manifest with the sudden onset of focal neurological deficits. In the largest surgical series of 100 brainstem CMs (Porter et al., 1999), 97% of the patients presented with focal neurological deficits related to hemorrhage. Even small hemorrhages in the brainstem, where lesions can be near critical nuclei and nerve tracts, may be poorly tolerated. The signs and symptoms depend on the exact location of the lesion within the brainstem but can include headache, motor weakness, sensory disturbances, nausea, vomiting, and equilibrium disturbances. Cranial nerve deficits, which include diplopia, swallowing difficulties, and alteration in voice quality, are also common manifestations. A hemorrhage in the brainstem may be associated with the subtle and gradual signs and symptoms, or it can be catastrophic. Death is rare unless patients have experienced multiple recurrent hemorrhages.

The effect of pregnancy on the behavior of CMs is still poorly defined. Studies have suggested that pregnancy may encourage an aggressive clinical course in women with CMs (Flemming et al., 2003; Maraire & Awad, 1995). However, too few cases have been reported to draw firm conclusions.

Diagnosis

Computed tomography usually detects the presence of a CM. It can show a hematoma or calcification, but it cannot differentiate the type of lesion (i.e., CM from tumor or other vascular lesions). Before the advent of magnetic resonance imaging (MRI), many CMs were missed or misidentified. CMs are most accurately diagnosed with MRI. The sensitivity for MRI as a diagnostic tool for the detection of CMs has ranged from 80% to 100%. The unique sensitivity of MRI defines the characteristics of CMs, allowing diagnosis without pathological examination (Feiz-Erfan et al., 2002).

Because CMs are low-flow lesions, they are not routinely detected on angiography. This modality is therefore inappropriate for the diagnosis of CMs. In fact, CMs were once called angiographically occult lesions. Before MRI was available, CMs were seldom diagnosed preoperatively. Histological analysis of surgical specimens provides the definitive diagnosis.

The familial form of the disease requires careful monitoring of all family members because de novo CMs have been noted (Zabramski et al., 1994b). They should be followed with serial MRIs each year or when new symptoms appear. If possible, surgery is recommended for patients with uncontrollable seizures, progressive neurological deterioration, or both. Genetic counseling of family members is strongly recommended.

Management

The most widely accepted standard of practice is surgical excision of CMs that are accessible. Indications for surgical management are hemorrhage, progressive neurological deficits, rehemorrhage, and seizures. Total resection, which eliminates further risk of rebleeding and neurological decline, offers patients a complete cure and is the treatment of choice. CMs that do not fulfill the criteria for surgical management, such as small lesions and those in noneloquent areas of the brain, may be managed conservatively by serial MRIs.

With each new hemorrhage, patients usually experience an increase in their level of neurological deficits. Even with recovery, patients seldom completely regain their neurological baseline. Further hemorrhages may mean a stepwise decline in neurological function that never returns to baseline. Therefore, the surgical goal is to remove the lesion, eliminating the threat of further hemorrhage and subsequent neurological decline. After surgical removal, patients may experience some degree of worsening similar to the effects of a spontaneous hemorrhage. Usually, however, this decline is transient, and most patients recover function over time.

Brainstem CMs are particularly challenging to resect because they occupy the most eloquent territory of the brain. Their management, however, is the same as for other types of CMs. These lesions are curable if surgery is feasible and if complete resection can be obtained. Again, the goal of surgery is to obliterate the lesion to avoid the risk of future bleeding. Because the brainstem involves so many critical life-sustaining functions, CMs there can be extremely challenging to remove safely. Therefore, resection of these lesions is reserved for neurosurgeons specially trained in skull-base approaches to brainstem surgery. As with any surgery, the risks involved must be weighed against the benefits. The choice will depend on the natural history of the specific lesion, the patient's status, and the surgeon's experience in treating brainstem lesions (Nakaji, 2005).

Patients must be considered individually to determine their best management option. Important factors include the presence of hemorrhage, neurological deficits, or seizures; the size and location of the lesion; the patient's age and medical history; and the surgeon's experience. If the overall morbidity and mortality rates associated with surgery are less than those associated with the natural history of the untreated CM, surgery is warranted. Consequently, patients with multiple lesions are often observed without pursuing surgery because multiple procedures compound their risks of a poor outcome. Likewise, the risks of surgery are high in patients with deep-seated lesions. With considerable experience, however, even very complicated lesions may be considered for resection (Nakaji, 2005).

The use of Gamma Knife radiosurgery in the treatment of CMs is controversial. Patients with lesions presumed to be high risk have been treated with radio-surgery. The findings suggest that this modality may reduce the risk of hemorrhage in this population. This reduction, however, was most pronounced after 2 years (Hasegawa et al., 2002). Other studies strongly suggest that radiosurgery not only fails to reduce risks but may actually increase the risk of rehemorrhage during the acute phase. Further research is needed to define the value of radiosurgery for the treatment of CMs. However, most surgical authorities recommend that its use be reserved for lesions considered inoperable, a category into which few CMs currently fall.

Nursing Implications

Caring for patients with a CM is both challenging and rewarding. Patients with a new diagnosis of CM frequently have neurological disturbances such as seizures or focal neurological deficits. Because CMs can occur anywhere in the central nervous system, patients can have a vast array of neurological symptoms. Especially challenging are CMs located in the brainstem, which can be devastating to both patient and family.

When seizures are newly diagnosed in a patient with a CM, the usual list of concerns associated with seizures applies. The most common issue is the use of antiepileptic drugs. Nurses need to instruct patients and their families about drug interactions, common side effects, and maintenance of therapeutic drug levels. Nurses must be prepared to discuss other common concerns related to seizures such as driving and overall safety precautions for the patient and the family.

The most important tool for the neuroscience nurse is assessment. Before a physical assessment is performed, an adequate medical history should be obtained (Table 2), with attention to family history. Next, a thorough neurological examination is performed. Cognitive, motor, sensory, cerebellar, and cranial nerve functions are all assessed. Knowledge of the location of the CM should lead the nurse to look for certain problems, such as dysphagia in a patient with a CM located in the lower brainstem.

As with most neurosurgical patients, immobility must be managed carefully. Patients with CMs rarely need to be restricted to bed rest. Therefore, early activity and ambulation are important. Prophylaxis for deep vein thrombosis, such as the use of anti-embolism stockings and subcutaneous heparin or enaparin, is encouraged in patients with limited mobility, for example, those with hemiparesis.

The patient's early involvement with therapy is important. When necessary, physical therapy, occupational therapy, and possibly speech therapy should be instituted early. Patients with brainstem CMs also should be assessed for swallowing difficulties as soon as possible. If needed, neurorehabilitation is encouraged. Most patients experience a decrease in neurological function after hemorrhage and surgery. However, they also usually improve, almost to their prehemorrhage baseline.

There are additional considerations with patients with the familial form of CM. Screening of other family members is strongly recommended. Siblings, children, and parents should all undergo MRI of the brain and spinal cord. Genetic counseling is recommended for those who have documented CMs or who have a strong family history of CMs or seizures.

The neuroscience nurse plays an invaluable role in the recovery and rehabilitation of patients with CMs. These patients, especially those with brainstem CMs, can experience devastating neurological decline. Although improvement is expected, it is usually slow and may be frustrating. Patients and families are better able to navigate through the course of this sometimes difficult condition when they understand the basic pathology and natural history of this neurovascular malformation. Because neuroscience nurses help educate and support patients and their families and help establish realistic goals, they are an integral part of the process of recovery and rehabilitation.

Conclusions

That the nursing literature devoted to CMs is limited suggests that the possibilities for nursing research are numerous. There are many areas of opportunity, including the consequences of neurological deficits, especially those because of brainstem CMs, on the quality of life. Difficulty with swallow or dysphagia can be especially challenging problems for patients with CMs. Many patients with dysphagia require intubation and temporary mechanical ventilation. Long-term solutions may be needed for patients who still require enteral feedings at discharge. Dysphagia and alternative methods of nutrition are nursing issues that invite further investigation. Considerable attention has been focused on the genetic aspects of CMs. However, related emotional, cultural, and social issues have not been explored and also represent opportunities for nursing research.

DOI: 10.1097/JNN.0b013e3181ecaf95

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Questions or comments about this article may be directed to Denita Ryan, RN ANP-C CNRN, at d2ryan@chw.edu. She is a nurse practitioner in the Division of Advanced Practice Nursing, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
TABLE 1. Comparison of AVMs and CMs

                                                 Intralesional
Type of        Incidence   Familial   Multiple   pressure
malformation   (%)         form       CMS        (mmHg)

CMS            0.4-0.5     Yes        Yes        38 mm

AVMs           1           Rare       Rare       100 mm

Type of        Diagnostic                    Intervening
malformation   study         Treatment       brain tissue

CMS            MRI           Surgery         No

AVMs           Angiography   Surgery,        No
                             radiosurgery,
                             endovascular
                             therapy

Note. AVM = arteriovenous malformation; CM = cavernous malformation.

TABLE 2. Critical Questions on Medical
History of Patients With a CM

What are presenting symptoms?
Does patient have a headache? If so, where is it located?
How long does it last? What relieves it?
Does patient have seizures? If so, what type? What are
  the characteristics? What seizure medications, if any,
  does the patient take?
Has the patient had a hemorrhage? If yes, is this the first?
How many other seizures or hemorrhages has patient had?
Where is the lesion?
What neurological deficits does patient have?
Has patient had surgery?
Does patient have other medical conditions (e.g.,
  diabetes or cardiovascular disease?)
Does patient take any medications?
Do any other family members have seizures, or
  documented CMs?
How is diagnosis affecting patient's family and personal life?

Note. CM = cavernous malformation.
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