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Paragangliomas

are neoplasms of the paraganglia. The paraganglia are small aggregates of cells derived from embryonic neuroepithelium that are distributed throughout the human body in close association with the autonomic nervous system. Historically, the paraganglia have been divided into chromaffin and nonchromaffin subtypes. The carotid bodies are the largest and best known of the nonchromaffin paraganglia, and along with paraganglia of the temporal bone, are the most frequent source of paragangliomas encountered by the neurosurgeon.
Paragangliomas of the carotid body and temporal bone are slowly growing hypervascular tumors that originate at the carotid bifurcation and in the temporal bone, respectively. Patients with carotid body paragangliomas typically present with a painless mass at the angle of the jaw, while those with a temporal bone paraganglioma usually present with gradual hearing loss and unilateral pulsatile tinnitus. With larger lesions of either type, multiple lower cranial nerve palsies are common, and 1 to 3 percent of these tumors produce catecholamines that may give rise to additional symptoms. Although paragangliomas haw a predominantly benign appearance histologically, they are invasive locally and, rarely, can metastasize. They can occur in multiple locations simultaneously, and at least some seem to be inherited. Multiplanar computed tomography (CT) or magnetic resonance imaging (MRI) is usually sufficient for making this diagnosis: therefore, angiography is usually reserved for outlining the blood supply to lesions that will be treated by embolization or surgical resection. Complete surgical excision is now possible for most carotid body and temporal bone paragangliomas and should be the goal for most patients. Radiation therapy, however, may be an appropriate and effective therapy for some patients.

Paraganglia: Structure and Function

Since their discovery, the structure and function of the carotid and temporal paraganglia have been debated. Naturally, this has led to an unfortunate proliferation of confusing synonyms being applied to these structures. More recently, however, the role of these structures as chemoreceptors in a diffuse neuroendocrine system has been revealed. This system incorporates several organs that contain peptide-producing cells derived from neuroepithelium that are characterized by amine precursor uptake and decarboxylation (APUD).

Anatomy

The carotid body is a vascular reddish brown structure, about the size of a grain of rice, located within the adventitia posteromedial to the bifurcation of the common carotid artery (CCA). Blood reaches the carotid body via a fibrovascular bundle, the ligament of Mayer, that runs from the posterior surface of the CCA to the inferior portion of the carotid body and supplies the normal carotid body with more blood by weight than the brain.

The carotid body is innervated by the intercarotid plexus and the carotid branch of the glossopharyngeal nerve, also called the carotid sinus nerve or the nerve of Hering. Both receive contributions from the glossopharyngeal and vagus nerves and from the superior cervical sympathetic ganglion. Although the major innervation of the carotid body is sensory, efferent innervation for vasomotor tone control and inhibitory feedback mechanisms has also been proposed.

The temporal bone paraganglia are smaller ovoid masses located in various regions of the temporal bones. These bodies do not have a precise anatomic location but are always found in association with the nerves of Arnold and Jacobson. In 88 temporal bones from +l patients. Guild found 248 temporal bone paraganglia. Most temporal bones had at least one paraganglia while some had as many as 12. Most of the temporal bone paraganglia ( 135 ) were found along the course of the tympanic branch of the glossopharyngeal nerve (Jacobson' s nerve) at its origin (14), in the adventitia of the jugular bulb (37), in the tympanic canaliculus, on the promontory (27), and distally along the lesser petrosal nerve 13. Fewer ( 113) were found in association with the auricular branch of the vagus nerve (Arnold's nerve) which runs a variable course. Most of the temporal bone paraganglia found along this nerve were located within the jugular fossa (81): the remainder were distributed distally along the mastoid canaliculi between the jugular fossa and the descending part of the facial canal (19), within the descending facial canal (7), or accompanying an aberrant branch of Arnold's nerve that passed external to the skull base between the jugular fossa and the stylomastoid foramen (6). The sex, race, or side studied appears to make no difference in the number or position of these bodies. The number of paraganglia seems to increase until the fourth decade of life and then to decline.

Both Arnold's and Jacobson's nerves are accompanied by branches of the inferior tympanic branch of the ascending pharyngeal artery. This vessel supplies blood to the normal temporal bone paraganglia. Neoplasms may recruit additional blood supply from a variety of other sources, however, The temporal bone paraganglia are innervated by Arnold's and Jacobson's nerves along with some branches from the superior cervical sympathetic ganglion.

Histology

The carotid and temporal paraganglia are indistinguishable histologically. Wide bands of cartilaginous connective tissue divide the parenchyma into lobules. Each lobule is nourished by a single arteriole and is divided into three to six cell nests. Each of these cell nests, called glomeruli of Zellballen, contains 20 to 40 cells of various types that are surrounded by a sinusoidal vascular network.

The parenchyma of the paraganglia consists of two primary cell types. These are best called type I and type II cells. Type I cells are more common and are typically round with indistinct cell borders. Type I cells may be further divided into light, dark, and pyknotic subtypes that may have different functions. The role of type I cells. however, remains unknown. Because they store a variety of biologically active amines, it is tempting to postulate that these substances are released in response to chemical changes in the blood. On the other hand, these chemicals could modulate other chemoreceptive nerve endings. Similarly. type I cells could act as interneurons. Type II cells are smaller and irregularly shaped. They are situated between the type I cells and the surrounding vascular sinusoids. These cells may act as glial-like sheaths for the type I cells.

Paragangliomas
Pathology

Operative specimens from carotid body or temporal bone paragangliomas are generally indistinguishable. Smaller tumors may be grooved by the carotid arteries while larger ones may have vessels imbedded in the sample. These tumors tend to be smooth and well circumscribed. They have a rubbery consistency, and the cut surface is usually homogeneous except for some occasional areas of necrosis, fibrosis, or hemorrhage.

Although paragangliomas of the carotid body and temporal bone are generally regarded as benign. they are histologically invasive and can rnetastasize. Typically, rates of malignancy of 3 percent for temporal bone tumors and 12 percent for carotid body tumors are quoted, although some reports quote rates as high as 30 to 50 percent. The definition of malignancy for paragangliomas is difficult to establish, however. These tumors tend to develop spontaneously in multiple locations and to recur frequently. On the other hand, paragangliomas may grow very slowly and often lack histologic changes characteristic of other malignant tumors. Only relatively recently was a reduction in the proportion of type II cells and a poorer staining of type I cells for S-100 and glial fibrillary acidic protein (GFAP) reported to be correlated with an increased tumor grade. Finally, although patients with metastatic paragangliomas may quickly succumb, their prognosis is completely unpredictable, and some patients with multiple metastatic lesions survive for several decades.

The nonchromaffin paragangliomas also have a familial tendency. An analysis of 15 pedigrees by van der Mey and colleagues found that paragangliomas were inherited in an autosomal dominant fashion but were transmitted almost exclusively by males. For example, an affected father resulted in 28 percent (23/82) of descendants (11 males and 12 females) being affected, while in families with an affected mother, the disease was reported in only one descendant with a questionable diagnosis. This pattern of inheritance is best explained by a hypothesis of genomic imprinting by which a maternally derived mutant gene that leads to the development of a paraganglioma is inactivated during oogenesis only to be reactivated during spermatogenesis in a subsequent generation. Overall, half the patients in this series had a positive family history.

As could be expected, a positive family history also places a patient at increased risk for developing a second primary paraganglioma. In this circumstance, up to one-third of patients will have a second paraganglioma. Multicentric paragangliomas, however, are discovered in as many as 10 percent of patients without a significant family medical history. The onset of these multicentric tumors may be synchronous or delayed by several decades. Bilateral carotid body tumors are the most frequently encountered example. These are followed in frequency by the combination of a carotid body tumor and a temporal bone tumor and then other combinations. Plurifocal tumors can occur in 3 to 5 percent of patients.

Clinical Presentation
Carotid Body Paragangliomas

Carotid body tumors are the second most frequently encountered nonchromaffin paragangliomas after temporal bone paragangliomas. More than 1000 cases have now been reported in the literature. These tumors usually present in patients in the fourth, fifth, or sixth decade of life, although reported cases range in age from 3 months to 89 years. An average tumor size is 4.5 x 3.5 x 3 cm, with the largest tumors exceeding 15 cm in diameter and weighing almost 200 g. There may be an increased incidence of these tumors in high-altitude dwellers, and although some reports show a female predominance greater than 5:1, carotid body tumors are less sex-specific than temporal bone paragangliomas.

Classically, carotid body tumors grow with progressive involvement of the internal and external carotid arteries, usually without constricting the arterial lumens. These lesions can extend into the base of the skull through a foramen or by bony erosion. Alternatively, they may grow medially or laterally and into the peripharyngeal space or inferiorly to invade the clavicle. The clinical manifestations of these tumors generally can be ascertained from these characteristic growth patterns. The widely accepted Shamblin classification system of carotid body tumors is primarily used for staging purposes, but also allows a comparison between different therapeutic modalities.

Patients with carotid body tumors typically present with a painless mass at the angle of the jaw that may be partially covered by the sternocliedomastoid muscle. Although many other possibilities exist in the differential diagnosis of such lesions (Table-1 ). Classically, the mass from a carotid body tumor is mobile laterally, but is restricted from vertical movement because of its attachment to the bifurcation of the CCA. These vascular tumors may transmit pulsations from the nearby carotid arteries or may be pulsatile inherently. The mass may shrink and re-expand spontaneously or with digital compression, and infrequently a bruit may also be heard over the mass. Larger tumors may produce a pharyngeal bulge that may displace or erode the tonsil, soft palate or uvula. In these instances, patients may present with spontaneous oropharyngeal bleeding. Occasionally, however, these tumors are discovered incidentally at angiography, surgery or autopsy.

TABLE-1 Differential Diagnosis of Carotid Body Paragangliomas

Lymphadenitis Fibroma. lipoma. hemangioma.
Lymphoma dermoid. teratoma
Branchial cleft cyst Aneurysm
Lymph node metastases Giant cell arteritis
Lateral aberrant thyroid Hematoma

Vagal or sympathetic neurogenic tumors

Carotid stenosis with poststenotic dilatation
Salivary gland tumors Carotid calcification

An invasion of surrounding neural structures in the neck can result in a variety of additional sequelae. At the time of diagnosis, cranial nerve palsies are usually present in less than 10 percent of patients. The vagus and hypoglossal nerves are most frequently involved, and this usually leads to dysphagia or hoarseness. Cranial nerves V and VII may also be involved, however. In addition, infiltration of the cervical or brachial plexus may result in the mass being painful or tender, while involvement of the cervical sympathetic chain can produce a Horner's syndrome. The distant effects of these tumors are varied and remain for the most part unexplained. Perhaps the best example of this phenomenon is the carotid sinus syndrome. This syndrome of bradycardia, hypotension, and a loss of consciousness may occur spontaneously or secondary to head movement or direct pressure on the tumor in some patients with carotid body paragangliomas. Additional reports of such systemic abnormalities that have resolved after tumor excision include alterations in gut motility with emesis on manipulation of the tumor, extensive skin alterations. constitutional symptoms such as weight loss and fever and even one case of membranous glornerulonephritis. Finally. while catecholamine production is exceedingly rare for extra-adrenal paragangliomas, a few patients with these tumors may present with a variety of symptoms or signs secondary to catecholamine production. Norepinephrine is the usual product and hypertension is the most frequent finding. Although only a handful of such cases have been reported in the literature, being unaware of functional tumors can have disastrous consequences during embolization or surgery. Therefore, patients with suspicious findings should have free norepinephrine, epinephrine. and 3,4-dihydroxy­phenylglycol measured in a 24-h urine collection. If these tests confirm the presence of such a tumor then the patient should undergo an appropriate adrenergic blockade prior to embolization or surgery (Table -2).

TABLE-2 Treatment Guidelines for Adrenergic Blockade a-Adrenergic Blockade

α-Adrenergic Blockade
At least 2 weeks before surgery, establish adequate blockade in all patients with norepinephrine- and epinephrine-secreting tumors.
Begin with phenoxybenzamine, 10 mg twice a day: increase by 10 mg/day at 3-day intervals: 10-20 mg 3 times a day usually suffices.
Maintain patient on generous salt diet to expand blood volume.
β-Adrenergic Blockade
Indicated in patients with a heart rate greater than 110 beats/min. history of arrhythmias or persistent ventricular extrasystoles. or predominantly epinephrine-secreting tumor: also in patients with pulse rate greater than 110 beats/min after initiation of phenoxybenzamine therapy.
For most patients. begin with propranolol. not to exceed 10 mg 3 times a day: 30-60 rug/day usually suffices. For patients with history of bronchospastic disease use low-dose metoprolol or equivalent cardioselective beta-blocker.
Do not initiate β-adrenergic blockade until α-adrenergic blockade is at least partially established.
Temporal Bone Paragangliomas

Temporal bone paragangliomas are the most frequently encountered benign tumor of the temporal bone, and must be considered in the differential diagnosis of temporal bone lesions (Table­3). Although frequent histologic misinterpretation, difficulties with nomenclature, and republication of cases make estimates of prevalence difficult, well over 1000 cases have been reported in the world literature. These tumors usually present in patients in the fifth decade of life, although reported cases range in age from 22 months to 85 years of age. Females with temporal bone paragangliomas outnumber males approximately 3 : 1 in most large series and ratios of 10: 1 have been reported. Larger studies also suggest a preference for the left side, especially in females.

TABLE-3 Differential Diagnosis of Temporal Bone Paragangliomas
  1. Otitis media

  2. Otosclerosis

  3. Chronic mastoiditis

  4. Cholesteatoma

  5. Cholesterol granuloma

  6. Eosinophilic granuloma

  7. Chordoma

  8. Vestibular schwannoma

  9. Meningioma

  10. Metastasis

  11. Aneurysm

  12. Aberrant intrapetrous internal carotid artery

  13. Idiopathic hemotympanum

  14. Arteriovenous malformation

  15. Prominent jugular bulb

  16. Persistent stapedial artery

Paragangliomas of the temporal bone are generally divided into those that originate within the middle ear, glomus tympanicum tumors, and those that originate within the jugular fossa. glomus jugulare tumors. This latter term, however, is often used to refer to large tumors where the origin is difficult to determine. The predominance of the paraganglia within the jugular fossa likely accounts for the increased frequency of tumors with this origin. Classification systems that have been developed for temporal bone paragangliomas are used for staging purposes. surgical planning, and comparison among different therapeutic modalities. The Glasscock-Jackson (Table-4) and Fisch (Table-5) classifications are the most widely employed.

TABLE 154-4 Glasscock-Jackson Classification of Temporal Bone Paragangliomas
  1. Type I Small tumor involving the jugular bulb. middle ear. and mastoid

  2. Type II Tumor extending under internal auditory canal: might have intracranial extension

  3. Type III Tumor extending into petrous apex: might haw intracranial extension

  4. Type IV Tumor extending beyond petrous apex into clivus or infratemporal fossa: might have intracranial extension

TABLE-5 Fisch Classification of Temporal Bone Paragangliomas
  1. Class A: Tumors limited to the middle ear cleft

  2. Class B: Tumors limited to the tympanomastoid area without destruction of bone in the infralabyrinthine compartment

  3. Class C: Tumors extending into and destroying bone of the infralabyrinthine and apical compartments of the temporal bone

  4. C1: Tumors destroying the bone of the jugular foramen and jugular bulb with limited involvement of the vertical portion of the carotid canal

  5. C2: Tumors destroying the infralabyrinthine compartment of the temporal bone and invading the vertical portion of the carotid canal

  6. C3: Tumors involving the infralabyrinthine and apical compartments of the temporal bone with invasion of the horizontal portion of the carotid canal

  7. Class D: Tumors with intracranial extension

  8. D1: Tumors with intracranial extension up to 2 cm in diameter

  9. D2: Tumors with an intracranial extension greater than 2 cm in diameter

  10. D3: Tumors with inoperable intracranial extension

The symptoms and signs that result from paraganglia of the temporal bone can be conveniently divided into otologic and neurological manifestations. Otologic symptoms usually predominate for both glomus jugulare and glomus tympanicum tumors. Unilateral hearing loss is the most frequent initial symptom and will be present in most patients. Typically it is gradual in onset, but an acute onset should not exclude the diagnosis. Although the hearing loss can be of the conductive type, sensorineural hearing loss is usually present at the time of diagnosis in most patients. This indicates involvement of the labyrinth or eighth cranial nerve and a poorer prognosis. Unilateral tinnitus, synchronous with the pulse, is the second most frequently reported symptom. Often, this is coincident with an audible bruit and both can be reduced with neck turning or direct pressure on the tumor. Otoscopic examination may reveal a gray-red mass in the external auditory canal or a hypervascular or bulging tympanic membrane. This mass may not be pulsatile on first inspection, but pulsations usually can be demonstrated by increasing the pressure within the external auditory canal using a pneumatic otoscope. Examination with the otoscope can also confirm bleeding from the lesion or an associated chronic otitis media that may lead to otalgia, meningitis or brain abscess. Neurological symptoms and signs generally follow otologic symptoms by several years, but ultimately these tumors produce neurological symptoms or signs in one-third to two-thirds of patients. These neurological findings are very important in classifying the stage and extent of these tumors. Neurological manifestations of these lesions result from involvement of either the cranial nerves or the brain. Although temporal bone paragangliomas can lead to a palsy of any adjacent cranial nerve, the facial nerve is the most commonly involved. The facial nerve may be affected in the middle ear or by extension of the tumor into the mastoid or internal acoustic meatus. In a similar way, vertigo may be secondary to involvement of the labyrinth, or secondary to compression of the eighth nerve directly. The resultant nystagmus is usually horizontal, but vertical and rotatory nystagmus have been reported. The lower cranial nerves are also frequently involved. Patients with glomus jugulare tumors often present with a jugular foramen syndrome that includes palsies of the ninth, tenth and eleventh cranial nerves. Greater cranial nerve involvement generally correlates with increased invasion of the nervous system and a worse prognosis.

Involvement of the central nervous system generally results from extension of the tumor into the middle or posterior cranial fossa, especially in the region of the cerebellopontine angle. Besides additional cranial nerve palsies, this can produce headache, increased intracranial pressure, cerebellar and long tract signs, or a Horner's syndrome. Seizures from temporal lobe penetration by a paraganglioma have been reported, and these tumors have been cited as the cause of cerebral ischemic events, congestive heart failure, and subarachnoid hemorrhage. A few patients with these tumors may also present with a variety of symptoms or signs secondary to catecholamine production as described above for carotid body tumors.

Radiographic Evaluation

Patients suspected of having a carotid body or temporal bone paraganglioma should undergo a noninvasive radiographic study to exclude more common entities and to detect an additional unsuspected paraganglioma at another location. The initial radiographic investigation selected depends on the clinical impression. Patients with a temporal bone paraganglioma thought to be limited to the middle ear (glomus tvmpanicum should undergo high-resolution, axial and direct coronal bolus-enhanced CT of the temporal bone and surrounding structures. A small glomus tympanicum tumor will appear as a contrast-enhancing soft tissue mass on the promontory within the middle ear cavity. If the bony septum that separates the jugular bulb and carotid artery from the middle ear is intact, then several vascular abnormalities within the differential diagnosis can also be excluded. Furthermore, any tumor present can be considered limited to the middle ear. This has considerable importance in selecting the appropriate surgical approach.

Patients thought to have a carotid body paraganglioma or a temporal bone paraganglioma that extends beyond the middle ear or that originates next to the jugular bulb (glomus jugulare) should undergo multiplanar, thin-section, T1- and T2-weighted and gadolinium diethylenetriaminepenta-acetic acid (DTPA) enhanced MRI. Paragangliomas have an intermediate signal on T1-weighted and a high signal on T2-weighted images and enhance intensely. In addition, paragangliomas greater than 2 cm in size produce a characteristic salt-and-pepper appearance that results from the fast-flowing blood pools and large tumor vessels within these lesions. Although this appearance in the petromastoid region is almost pathognomonic for a temporal bone paraganglioma, renal and thyroid carcinoma metastases and hemangiomas can be confused with carotid body paragangliomas in the peripharyngeal space. Although MRI clearly proves involvement of the carotid arteries and jugular vein by these lesions, bony land­marks in the skull base are poorly defined by MR images. and parallel imaging with CT may be necessary.

Cerebral angiography remains the gold standard for the diagnosis of head and neck paragangliomas, but in practice, this study is reserved for patients who have larger tumors and who are scheduled for embolization or resection. The main goal of angiography in such patients is to delineate the vascular anatomy of the tumor. However, it can also be used to determine the presence of internal carotid artery invasion and to evaluate for atherosclerotic disease, patency of the circle of Willis. and the patient's tolerance of balloon test occlusion. Both external carotid artery (ECA) and internal carotid artery (lCA) iodinated contrast injections are routinely employed. If intracranial extension is suspected, vertebrobasilar angiography will also be necessary.

Paragangliomas have an angiographic appearance midway between that of a meningioma and that of an arteriovenous malformation. Early phases show variably sized pathologic vessels around the tumor site. This is followed by an intense, occasionally inhomogeneous staining of the tumor. For temporal bone tumors such a tumor blush appears in the middle ear and may be obscured by the overlying temporal bone. Thus, subtraction techniques may be necessary. Other findings with temporal bone paragangliomas may include an increase in the number and size of branches passing from the ECA to the temporal bone and displacement of vessels within the middle or posterior cranial compartment. Besides the characteristic tumor blush in patients with a carotid body tumor, a characteristic distortion of the carotid bifurcation is also visible on angiography. The ICA is generally pushed laterally and posteriorly while the ECA is displaced anteriorly.

Other diagnostic techniques may also be of value if applied under appropriate circumstances. For example, about half of all head and neck paragangliomas can be detected using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. Most nonchromaffin paragangliomas show low uptake of this tracer: therefore, single photon emission computed tomography (SPECT) images are needed to eliminate the interference created by the normal uptake of tracer in the parotid and submandibular glands. In addition, total body scintigraphy with 123I-MIBG can be used as a screening tool to detect distant additional primary or metastatic lesions in patients or their near relatives. Although it is often speculated that such uptake, especially if intense, suggests a norepinephrine­producing tumor, the uptake of 123I-MIBG can be independent of catecholamine secretory activity. In lesions that show tracer up­take, this technique can be used to document the results of therapy or to treat unresectable lesions by using radiotherapeutic doses of 131I-MIBG. Color Doppler ultrasound can also be used to demonstrate vascular lesions that disrupt the carotid bifurcation, but it will not reliably differentiate between carotid body tumors and other vascular lesions in the area.

Treatment

There are four treatment options for patients with carotid body or temporal bone paragangliomas. These can be used alone or in various combinations. The ideal treatment for most patients is complete surgical excision of the tumor. Endovascular embolization can be used preoperatively to facilitate such a resection, but insufficient evidence exists to warrant its isolated use. In patients not suited for operative therapy, irradiation may be a useful measure for primary or metastatic disease. Chemotherapy, on the other hand, has been reserved for patients with systemic metastases and has no proven efficacy except for a few isolated case reports.

Embolization

Endovascular embolization of carotid body or temporal bone tumors may reduce operative time and limit blood loss. This was shown in one representative work by Ward and colleagues who retrospectively compared six patients with carotid body tumors who underwent preoperative embolization to ten patients with 11 tumors who did not. They found a reduction in average operative time from 4.24 h to 1.75 h. The blood loss was also reduced from 1250 ml to approximately 400 ml. Although these authors also observed a reduction in operative cranial nerve injuries in patients who underwent preoperative embolization. they provide no basis for comparison between the two groups for other important parameters such as tumor classification or size. Similarly, Murphy and Brackmann reported a series of patients with temporal bone tumors stratified according to the Fisch classification system. Eighteen patients underwent preoperative embolization while 17 patients did not. When patients with tumors from all classifications were grouped together, embolized patients showed a significant reduction in operative blood loss from 2769 ml to 1122 ml (p < 0.005) and a reduction in operative time from 7.95 h to 7.04 h (p < 0.005). However, Murphy and Brackmann could not show a reduction in postoperative cranial nerve deficits with embolization. In both of the above studies, however, the embolized patients were always later in the series. Therefore, these conclusions are confounded by other variables such as an increase in the experience of the operative team. Although some authorities have not found preoperative embolization necessary, most now employ this technique for Shamblin type III carotid body tumors and Fisch type C2.3 or D temporal bone tumors. Embolization usually takes place immediately following the diagnostic angiogram and is then followed soon after by surgery to prevent the recognized phenomena of collateral vessel formation and recanalization.

Temporal bone paragangliomas may be composed of up to four hemodynamically isolated compartments. Each of these compartments is primarily supplied by different branches of the ECA. Therefore, superselective catheterization of specific branches of the ECA is necessary for complete embolization of a multicompartmental tumor. Blood supply from the internal carotid and vertebral arteries can be shown for some anteriorly located tumors that may be supplied by the caroticotympanic branch of the ICA. Large tumors with extradural intracranial extension may also be supplied by clival and cavernous branches of the ICA. The intradural component of Fisch type D, tumors is always supplied by parenchymal branches from the vertebrobasilar system, usually the posterior inferior cerebellar artery at the level of the jugular foramen and the anterior inferior cerebellar artery in the cerebellopontine angle.

Complete devascularization of Fisch type C and at least partial devascularization of type D tumors can usually be achicved. Tumors with an anterior component supplied by the caroticotympanic artery can be embolized completely only if this artery can be selectively catheterized and there is no evidence of contrast reflux into the ICA. Otherwise tumors with significant ICA blood supply can only be embolized by balloon occlusion of the petrous ICA provided the patient has tolerated temporary balloon occlusion and hypotensive testing before embolization. The intradural portion of type D tumors is supplied by the vertebrobasilar system and cannot be embolized safely.

Preoperative embolization of temporal bone paragangliomas is usually followed by a fever and transient ear pain. This procedure may also be complicated by wound healing problems, cerebral ischemia, and lower cranial nerve palsies. Ischemic cerebral events are most likely to occur if arterial anastomoses exist between the branches of the ECA supplying the tumor and the ICA or vertebrobasilar arterial system. Such anastomoses, present in as many as one-third of patients, are not a contraindication to embolization, but special techniques such as temporary occlusion of the anastomotic artery or the use of embolic particles larger than the anastomotic artery must be employed. Similarly, permanent new cranial nerve palsies may develop if nonabsorbable embolization material is injected into the neuromeningeal branch of the ascending pharyngeal artery that supplies cranial nerves IX through XII or the stylomastoid and middle meningeal arteries that supply blood to cranial nerve VII. Absorbable materials such as Gelfoam may still produce cranial nerve palsies, but these are usually transient.

Preoperative embolization of carotid body tumors follows the same basic principles as outlined above for temporal bone paragangliomas. Most carotid body tumors are also multicompartmental, with the bulk of the blood supply coming from the ascending cervical artery and the musculospinal branch of the ascending pharyngeal artery. The tumor may also be supplied by the facial, lingual, thyroid, posterior auricular, occipital, and deep cervical arteries. The artery of the carotid body that also supplies these tumors cannot usually be identified on angiography, and therefore cannot be embolized.

Radiation Therapy

Opinions vary on the value of radiation therapy in the treatment of the paragangliomas of the carotid body and temporal bone. The debate centers on the radiosensitivity of these tumors. Histologically, radiation results in edema, fibrosis, hemosiderin pigmentation and degeneration of the vessel walls with intimal proliferation leading to partial obliteration and thrombosis. It seems not to affect the cellular elements of the paragangliomas, however, with most tumors retaining many areas that appear viable.

Unfortunately. there are no generally accepted criteria for successful radiation therapy of these lesions. While some authors claim that all patients treated with radiation therapy obtain symptomatic relief, few report significant regression of the tumor mass and no evidence exists to show that local irradiation decreases the risk of developing metastases. To evaluate the results of radiation therapy for these lesions. Springate and colleagues reviewed the literature on the treatment of temporal body paragangliomas published from 1965 to 1988. In this review, all patients without evidence of disease progression on clinical or radiographic examination were considered to have been treated successfully. Using this definition, they averaged the cases reported in the literature and found success rates of 86. 90. and 93 percent for surgery alone. irradiation with or without surgery, and irradiation alone, respectively. While such a comparison is used to advocate radiation therapy as a primary treatment for head and neck paragangliomas, it fails to recognize that the goal of surgical therapy, that is, eradication of disease, is different from the goal of radiation therapy, which is limitation of disease progression. As a result, no valid comparison between radiation and surgical therapy exists in the literature.

Despite these concerns, radiation therapy for patients with carotid body or temporal bone paragangliomas leads initially to symptomatic relief in most patients. Neurological deficits, however, are rarely relieved and may progress after irradiation. For example, Cummings and colleagues reported on a series of 45 patients who received radiation therapy for temporal bone paragangliomas. In this group, most patients were relieved of tinnitus (30/38), pain (8/8), and vertigo (5/5), although this was sometimes delayed for several months. Furthermore, these symptoms recurred in only three patients during a follow-up period that ranged from 3 to 23 years. In contrast, only two patients had significant relief of cranial nerve deficits. Similarly, Valdagni and Amichetti reported on 13 carotid body tumors in seven patients followed from 1 to 19 years after Irradiation. While no patient in this series was considered to have progressive disease, only three tumors displayed regression and only seven patients had symptomatic relief.

Complications secondary to radiation therapy for temporal bone paragangliomas are generally more severe than those encountered during the treatment of carotid body tumors. The most serious sequelae from radiation of temporal bone paragangliomas include brain and temporal bone necrosis that may be life-threatening. This complication is reported in one or two patients in most series, for an average of slightly less than 4 percent. These patients have almost always received more than the standard 3500­5000 rad megavoltage dose given via a homolateral wedge pair technique over 3 to 5 weeks in most centers. Other less severe complications associated with temporal body paraganglioma irradiation include protracted otorrhea or otitis, vertigo, ataxia and external auditory canal stenosis. Although the complications associated with carotid body tumors are infrequent and generally trivial, radiation therapy may result in delayed hemiplegia, postradiation stricture of the larynx, and radionecrosis of the carotid artery and mandible. Such radiation will also complicate subsequent surgery. Therefore, radiation therapy as a treatment should be limited to patients who are elderly and asymptomatic, who have undergone incomplete resection, who refuse surgery, or who develop recurrent or metastatic lesions. Patients who have bilateral paragangliomas with severe cranial nerve deficits, especially of the glossopharyngeal and vagus nerve on one side secondary to tumor progression or surgical excision, should also be considered for radiation therapy. Experience is now accumulating with the radiosurgical treatment of temporal bone paragangliomas. Time will tell whether this approach is better than conventional radiotherapy.

Surgical Therapy:
Carotid Body Paragangliomas

Complete surgical excision remains the preferred treatment for most patients with carotid body tumors. This is especially true for tumors that display aggressive or invasive growth locally. Small tumors, tumors that interfere with normal function and tumors in young people should also undergo surgical removal. With advanced techniques, including intraoperative cerebral blood flow and electroencephalographic monitoring; lCA shunting, grafting or reconstruction; and mobilization of the parotid gland: nearly all carotid body tumors can be resected completely with small risk of stroke or death. For example, among 30 cervical paragangliomas, mostly Shamblin type II carotid body tumors, resected between 1976 and 1986, Hallett and colleagues reported only one stroke and no deaths.

Postoperative cranial nerve deficits and arterial injury, however, have remained a significant problem. While only 10 percent of patients in the above series were found to have cranial nerve deficits preoperatively, this number increased to 40 percent postoperatively. Fortunately, these deficits were transient in one-half of these patients. The most frequently affected nerves were the hypoglossal nerve and the vagus nerve. The superior laryngeal nerve and the pharyngeal branches of the vagus nerve were especially at risk. Less frequently injured were the glossopharyngeal and spinal accessory nerves, the sympathetic chain, and the mandibular branch of the facial nerve. More than one of these nerves was injured in roughly one-third of these patients. In this same series, 33 percent of patients required ligation or resection of the ECA. The lCA required reconstruction in 25 percent and was directly repaired in an additional 9 percent. The carotid arteries were temporarily clamped in 9 percent. Patients in this series who underwent arterial repair required significantly more transfused blood (5.67 U versus 1.92 U) and had a higher complication rate.

Patients with larger tumors tend to have a higher incidence of cranial nerve and arterial injury. Other complications resulting from the surgical therapy of these lesions are infrequent but may include venous graft occlusion, hemorrhage, internal carotid artery spasm, and respiratory failure secondary to aspiration. Preoperative embolization, especially for larger tumors, may reduce these complications

The basic principle behind successful surgery for carotid body paragangliomas is preoperative preparation and early intraoperative identification of neural and vascular structures. This can be achieved by using a wide exposure, intraoperative monitoring of cerebral blood flow and electroencephalographic activity, peri adventitial tumor dissection in an inferior to superior direction, appropriate grafting or shunting of the lCA, appropriate parotid gland mobilization, and meticulous haemostasis and microtechnique.

The patient is placed supine on the operating table and general anaesthesia is induced. A nasoendotracheal tube is used to allow maximal upward displacement of the floor of the mouth. The operative field that extends from the clavicle to above the superior extension of the pinna of the ear is then prepared. Routinely, the ipsilateral lower extremity is also prepared for saphenous vein harvesting. Although for cosmetic considerations a high horizontal incision may be used for very small tumors. typically a vertical incision is used. Tumors that extend into the posterior fossa should be approached by a separate suboccipital craniectomy.

The initial goal of the operation is to identify specific neural and vascular structures. The distal lCA is isolated first. This requires mobilization of the parotid gland. Therefore. once the skin incision has been made, the superficial cervical fascia is opened and the posterior border of the parotid gland is elevated. The temporoparotid fascia between the parotid gland and the mastoid process is then incised and the main trunk of the facial nerve is identified. The lower division of the facial nerve and the marginal mandibular nerve are dissected free and the deep cervical fascia is divided. The parotid gland is then gently retracted superiorly. The digastric muscle, stylohyoid muscle and stylomandibular ligament are then divided in turn to expose the distal lCA. The proximal CCA is then exposed and loose rubber tourniquets are placed around the lCA, ECA and CCA. Some authorities recommend obtaining baseline preocclusion and occlusion 131xenon cerebral blood flow measurements at this point in case rapid occlusion of the lCA is required later for hemostasis. Next, the neural elements are identified. The submandibular dissection is continued and the course of the vagus nerve is identified (it may be incorporated within the tumor bed). The hypoglossal nerve, which is usually displaced posterosuperiorly, and the spinal accessory nerve are also identified proximal and distal to the tumor and are tagged.

Tumor dissection begins by outlining the superficial medial and lateral margins of the tumor. Major arterial and venous feeding and draining vessels are identified and occluded. A peri adventitial tissue plane is developed near the bifurcation of the CCA at the lower end of the tumor. This allows coagulation of numerous vasa vasorum in this area that supply much of the blood supply of the tumor. Once the tumor has been at least partially devascularized, the superolateral portion of the tumor is mobilized away from the cranial nerves and the lCA under magnified vision. Finally, the posteromedial subadventitial attachment of the tumor is elevated and the superior laryngeal branch of the vagus nerve is dissected free. Great care must be taken in this region not to inadvertently enter the carotid artery. While temporary occlusion of the carotid artery or intravascular shunting is used routinely by some authors, it is usually not necessary. Once the tumor is removed, the arterial walls are inspected carefully and cerebral blood flow may be measured again. The incision is then closed in anatomic layers, incorporating multiple closed suction drains.

Surgical Therapy:
Temporal Bone Paragangliomas

The particular surgical approach used to resect temporal bone paragangliomas depends on the location and extent of the tumor. Paragangliomas originating from the promontory of the middle ear and isolated to the mesotympanum can be resected by elevating the tympanic membrane and removing the tumor using microdissection techniques. If the tumor extends into the hypotympanum or the mastoid, a tympanomastoidectomy is performed and the tumor resected.

Larger tumors that involve the jugular bulb or extend medial to the jugular bulb require more extensive dissection. Fortunately, with recent advances in the techniques of skull base surgery, extensive temporal bone paragangliomas can be resected completely by an experienced multidisciplinary team. For example, Jackson et al. reported on the treatment of 49 patients with skull base tumors with intracranial extension of which 36 were paragangliomas originating in the temporal bone. In this series of formidable tumors, 76 percent of patients had gross total tumor resection and most of those with incomplete removal were operated on early in the series. Now, according to these authors, tumors that involve the ICA or basilar artery, the foramen magnum, the cavernous sinus, or the clivus should no longer be considered unresectable.

Unfortunately, accurate data regarding the ability of surgery to cure these tumors are not available. Among those patients in the series referred to above with complete resection of a temporal bone paraganglioma, there were two recurrences after a mean follow-up of 5.1 years. One patient with incomplete resection accounted for another recurrence. Another series reported a single recurrence among 17 patients with temporal bone paragangliomas, but the follow-up time was not clearly stated. Still, these tumors usually grow slowly, and recurrent disease cannot be excluded for many years after surgical intervention. Therefore, meaningful results about the effects of aggressive modern surgical techniques on temporal bone paragangliomas will not be available for another decade or more.

Such aggressive resections in patients with larger tumors. however, are not without significant risk of complications (Table-6). For instance, in the series of Jackson et al., which is representative, 5 of the 49 patients died within 1 year of surgery. Further­more, only 24 percent of patients escaped cranial nerve deficit with 47 percent of patients sustaining injury to the ninth and tenth cranial nerve complex. No patient in this series, however, required permanent tracheostomy or gastrostomy tube alimentation. Enhanced neural preservation can be achieved with smaller lesions and this underscores the need for early diagnosis and treatment of these lesions. Irradiation prior to surgery may also curtail cranial nerve preservation. A number of approaches to temporal bone paragangliomas have been described. Most of these are used to excise tumors without intracranial extension or as the first part of a two-stage operation where an intracranial tumor is removed through a separate suboccipital craniectomy. More recently, a number of combined approaches have been developed that allow tumors with a large intracranial component to be resected by a multidisciplinary team during a single operation.

TABLE-6 Representative Operative Complications and Outcome from Resection of Temporal Bone Tumors

  • Mortality                           8%

  • Tumor recurrence               8%

  • Wound infection                11%

  • Cerebrospinal fluid leakage   20%

  • Meningitis                         8%

  • Required treatments

  • Vocal cord injection            23%

  • Tracheostomy                    8%

  • Tarrsorrhaphy                    19%

After general anaesthesia is induced, the patient is generally placed on the operating table in the supine position. The shoulder is then elevated to a variable degree depending on the location of the tumor or the preference of the surgeon. A more lateral position allows excellent exposure of the posterior fossa component of the tumor but compromises tumor removal from the neck and skull base. A nasoendotracheal tube is used to allow maximal upward displacement of the floor of the mouth. The pre- and postauricular areas and the neck are prepared from the clavicle to above the superior extension of the pinna of the ear. Routinely, the ipsilateral lower limb is also prepared for saphenous vein and fascia lata harvesting. The abdominal area is also prepared as a site for adipose tissue donation.

A postauricular curvilinear incision is then made. This may be extended in either direction to improve exposure. As this flap is retracted, the external auditory canal is transected and closed as a blind sac. The attachment of the sternocliedomastoid muscle and the contents of the carotid sheath are then identified. The base of the skull that lies behind and lateral to the jugular foramen must then be exposed fully. This requires that the sternocliedomastoid muscle and the underlying splenius and suboccipital muscles be dissected off the base of the skull. Care must be taken in this step to avoid injury to the vertebral artery. The dissection is continued until it merges with one proceeding upward from the neck that has exposed the internal jugular vein, ICA, ECA and the nerves of the jugular foramen.

The majority of the patients had intracranial tumor extension. Smaller tumors are associated with fewer complications.

Here the surgeon must avoid injury to the inferior petrosal sinus that may merge with the internal jugular vein after it exits the skull. Branches from the ECA that are supplying the tumor, usually the ascending pharyngeal, posterior auricular, and occipital arteries are occluded. and vascular tapes are secured around the internal jugular vein, ICA and ECA.

The second stage of the operation requires the use of a high-speed drill to perform an extensive mastoidectomy. First, the mastoid process is removed, and then the sigmoid sinus and the bony labyrinth are skeletonized. If the tumor extends along the ICA toward the petrous apex, the facial nerve is uncovered from the geniculate ganglion to the stylomastoid foramen and transposed anterosuperiorly out of the fallopian canal. A suboccipital craniotomy or craniectomy is then performed. The portion of the sigmoid sinus above the tumor is identified. and a ligature is passed through the dura and around the sinus in this location. A pair of similar ligatures are also placed around the internal jugular vein (below the tumor) and the vein is then transected between them. The lateral wall of the sigmoid sinus may be opened and any tumor invading this wall resected.

Attention is then turned to the ICA. It is followed up toward the skull base and into the petrous canal. This may require transection of the posterior belly of the digastric muscle and the stylohyoid muscle. Simultaneously, the lateral wall of the bony eustachian tube is drilled until the isthmus is identified, at which point the lumen is closed with bone wax and a fascial graft. The tumor is then mobilized progressively from various directions. As the superior pole of the tumor is drilled free, one must guard against opening into the basal turn of the cochlea or damaging the seventh and eighth cranial nerves. Finally, the jugular vein is lifted out of the neck and excised along with the lateral wall of the jugular bulb. Here the medial aspect of the tumor is carefully dissected from the cranial nerves. As this dissection proceeds, the inferior petrosal sinus with its multiple openings will be encountered and should be occluded. Finally, the extradural portion of the tumor is then divided from the intradural portion and removed.

The intradural portion of the tumor is then excised. First the dura is opened behind the sigmoid sinus. Meticulous haemostasis must then be maintained as the tumor is separated from the parenchyma of the brain. If the tumor encroaches on the anterior compartment of the jugular foramen. the cranial nerves in this area may not withstand the manipulation required for complete tumor removal. Therefore, in this instance, the goal of complete tumor removal must be weighed against neurological deficit. The same situation occurs when one encounters tumor that extensively involves the ICA, basilar artery, clivus, foramen magnum, or cavernous sinus.

Once the intradural component of the tumor has been removed, the wound is closed. Fascia lata may be used as a dural graft. The cavity is then obliterated with adipose tissue. A vascularized temporalis muscle flap can be swung inferiorly and sutured to the operative margins. The skin is then closed in several anatomic layers incorporating several closed suction drains. Adjunctive procedures thought to be necessary such as the insertion of a parenteral feeding catheter, insertion of a lumbar cerebrospinal fluid drainage catheter, tracheostomy, or insertion of a feeding gastrostomy tube are then completed.


Glomus jugulare tumors  are among the most difficult tumors arising in the base of the skull and considered the most challenging for surgical treatment, since the patients usually come to surgery in advanced state, after failure of adjunctive treatment  such as embolization, radiotherapy or previous attempts for partial resection. The neurological state of the patients was usually with involvement of the caudal group of nerves and even with infiltrative destruction of the facial nerve in several cases.

During the period of 1980-2004 I had the experience with 10 cases of what could be considered by Ugo Fisch & Douglas Mattox as class C4De2Di2 tumors.  For the academic pools and data concerning these tumors you can  follow the references. Here, the main concentration is directed to the  personal experience of difficulties during operative and the postoperative period.  One case was mentioned in the article: AVOIDANCE OF COSMETIC DEFORMITY IN APPROACHING THE PETROCLIVAL REGION DURING  COMBINED  TRANSPETROSAL APPROACH.

Case Presentation:

A young married women 27 years age came to the clinic 30-04-2003, complaining of severe headache for more than 3 years duration with hearing loss in the left ear for more than 2 years, ataxia for 11 months, swallowing difficulty for 9 months and complete left facial paralysis of peripheral type for 4 months with right sided hemiparesis and hypalgesia. MRI performed 22-07-2001 showed a mass in the left jugular bulb extending to the sigmoid and transverse sinuses left side. Attempt  for embolization  caused visual field scatomas . MRI done 12-01-2003 showed enlargement of the tumor  four times in volume. The patient  on examination, beside the above mentioned complains  showed severe atrophy of the left side of the tongue  with uvula sagging to the right in gag reflex. It was impossible to perform Romberg test due to inability of the patient  to stand. Slight paresis of the left abducens nerve was noted and the voice was dysphonic.

 Angiogram during embolization  

Preoperative  angiogram and MRI  showing the glomus jugulare tumor  shifting the brain stem and totally destroying the  left middle and inner ear structures.

 VIDEO RECORDING OF THE CASE

The patient was admitted to Al-Shmaisani hospital in Amman - Jordan and operated 17-05-2003. Using the modified transotic  translabyrinthine approach with preservation of the mastoid shell as described  elsewhere, it was possible to track the facial nerve, which seemed to be completely destroyed by the tumor. The inferior margin of the approach was extended to expose the IJV, which was checked for patency. It turned to be completely occluded and after its ligation below the involved mass, it was opened. resection of that part was achieved.

The facial nerve at its emergence from the brainstem was anastomosed using sural nerve  to the postfallopian part. To achieve good alignment of the proximal part , 2 hours spent to put three  10 zero nylon stitches. Using artificial tubes , was impossible due to insufficient length of the proximal part. The dura was closed leaving intentionally small defect to the anastomosis, to avoid mechanical pressure and the defect was glued by small piece of muscle. A muscle was harvested from the lower abdomen  with fat to fill the spaces under the bone flap , which was reflected  back and closed.

The operation took more than 20 hours and the patient required  16 units of blood and 12 units of FFP. Postoperative period was surprisingly  unremarkable and she was not in need for tracheostomy, which was highly suspected. NGT feeding was continued for 2 weeks, due to deterioration of the caudal group of nerves , as usual and the left abducens nerve became completely paralyzed after the operation, despite the fact, that it was not touched or violated during surgery. You can refer here! for more details.

 

 

 

 

 

 

 

MRI, MRA, MRV of the patient performed 28-07-2003 demonstrating the radical resection of the tumor and bone flap holding the muscle harvested from the quadriceps muscle

The patient was seen several times  at ambulatory  first with stitch sinus  and the left abducens was completely paralyzed. The patient then slowly, but steadily showed marked recovery of her hemiparesis , hypalgesia and the left trapezius  became more stronger . The abducens became fully functional  after four months. The atrophy of the left side of the tongue regressed and the swallowing and speech dramatically improved. After  9 months the facial nerve start to show dramatic signs of recovery. The patient came 12-12-2004 with almost complete recovery of her facial nerve function.

 

Discussion:

Conclusions:

 

References:

Jon H. Robertson, M.D., Jason A. Brodkey, M.D. Glomus Jugulare Tumors. The Practice of Neurosurgery. GeorgeT. Tindall, Paul R. Cooper & Daniel L. Barrow. Volume 1. 67: 1005-1020.

Ugo Fisch & Douglas Mattox: Classification of Glomus Temporale Tumors in  Microsurgery of the Skull Base . Thieme 149-153.

 

The author have made every effort to trace the copyright holders for borrowed material. If inadvertently overlooked any, will be pleased to make the necessary arrangements at the first opportunity.


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