Clinical Reasoning: A 51-year-old woman with syncopal episodes and multiple cranial neuropathies
Ioannis Karakis, MD,
Rodica E. Petrea, MD,
Janice F. Wiesman, MD and
Scharukh Jalisi, MD
From the Departments of Neurology (I.K., R.E.P., J.F.W.) and Otolaryngology-Head and Neck Surgery (S.J.), Boston University Medical Center, MA.
Address correspondence and reprint requests to Dr. Ioannis Karakis, Boston University Medical Center, 715 Albany Street, C 329, Boston, MA 02118 ioannis.karakis{at}bmc.org
Case presentation.
A 51-year-old right-handed woman was admitted to the hospitalbecause of two syncopal episodes. Both events had similar featureswith sudden onset of loss of consciousness. There were no precedingsymptoms. They lasted only few seconds and were not accompaniedby any abnormal movements, incontinence, or tongue biting. Therewas no confusion following the events. A feeling of vertigo,which gradually dissipated over the following 2 days, was theonly residual symptom following both episodes.
The patient also had a history of hypertension. She was on nomedications. She consumed alcohol occasionally but denied tobaccoor drug abuse. Her family history was positive only for heartdisease in her mother.
Question for consideration:
What is the differential diagnosis of syncope in this case?
Syncope is a sudden and brief loss of consciousness, associatedwith a loss of postural tone, with spontaneous recovery. Itresults from transiently decreased or interrupted cerebral bloodflow. Frequently, the etiology remains unknown. Among diagnosedcases, neurocardiogenic syncope (including vasovagal attack,situational syncope, and carotid sinus syncope) is the mostfrequent cause. It stems from reflex-mediated changes in thevascular tone or heart rate. Other causes include cardiac (organicheart disease or arrhythmia) or neurologic diseases (concussionor seizure), orthostatic hypotension, medications, or psychiatricdisorders.1,2 In this patient, based on the history, both reflex-mediatedand primary cardiac causes were contemplated.
On admission, the patient reported 3 years of right hearingdefect without tinnitus or ear pain. She denied dysphagia orhoarseness of her voice. She was otherwise asymptomatic.
On neurologic examination, cranial nerves I–VII were intact.There were multiple lower cranial neuropathies (VIII–XII)on the right side. There was sig-nificant right ear hearingloss. The tuning fork tests were equivocal: the Weber test lateralizedto the affected ear (suggesting a conductive hearing loss inthe right ear) and the Rinne test indicated air greater thanbone conduction on the right side (suggesting a sensorineuralhearing loss in the right ear). Her gag reflex was weaker onthe right side. The right sternocleidomastoid was atrophic andthere was winging of her right scapula. The right side of hertongue was mildly atrophic and exhibited prominent fasciculations(video 1). The remainder of the neurologic examination was unremarkable.
The otorhinolaryngologic examination was remarkable for a reddishhue behind the right tympanic membrane and mildly sluggish abductionof her right true vocal cord (video 2). The vocal cords hadgood approximation on phonation and swallowing suggesting compensationfrom the left true vocal cord. A formal audiogram was obtainedto elucidate the discrepancy of the tuning fork test and identifiedprofound sensorineural hearing loss in the right ear.
Question for consideration:
What is the differential diagnosis of multiple cranial neuropathies?
In a large series of multiple cranial nerve palsies, tumorscomprised 30% of the cases, followed by vascular disease (12%),trauma (12%), infection (10%) and Guillain-Barré syndrome(6%). Most commonly, a schwannoma (17%) was the culprit, followedby metastases (16%), meningioma (13%), lymphoma (10%), and pontineglioma (9%). The cranial nerve damage was usually at the cavernoussinus (25%), and less frequently at the brainstem (21%), thenerve itself (18%), the skull base (13%), and the subarachnoidspace (10%). The affected cranial nerves varied depending onthe etiology and the location of the damage, but the cranialnerves VI, VII, V, and III were most commonly involved in descendingorder of frequency.3
In this patient, the history of a hearing defect 3 years agoand the presence of atrophy and fasciculations in her tonguepointed more to a chronic condition than a vascular event. Therewas no clinical suspicion of trauma or infection. Thus a slowgrowing neoplasm appeared the most plausible explanation ofher multiple cranial neuropathies. The involvement of the cranialnerves VIII–XII only on the right, without long tractsigns, pointed toward skull base localization.
The patient had a negative cardiac evaluation (telemetry andechocardiogram) for her syncope. She had an unremarkable EEG.CT of the head showed a hyperdense mass at the right jugularforamen with associated destruction of the temporal bone (figure 1).
Jugular foramen tumors are classified as primary (i.e., locatedin the jugular foramen and extending into the adjacent structures)and as secondary (i.e., extending from the adjacent structuresinto the jugular foramen). In descending order of frequency,glomus jugulare tumors, schwannomas, and meningiomas are themost common primary tumors. The secondary tumors comprise chordomas,chondrosarcomas, chondroblastomas, giant cell tumors, cholesterolgranulomas, giant cholesterol cyst, endolymphatic sac tumors,reactive myofibroblastic tumors, temporal bone carcinomas, andmetastases. In the group of primary tumors, glomus jugularetumors can cause destruction of the jugular foramen margins,may have "salt-and-pepper" appearance in the T1 and flow voidson T2-weighted images, exhibit drop out effect with contrastadministration, and are hypervascular lesions with large feedingvessels and early draining veins seen on angiography. Schwannomascan cause foramen enlargement without invasion, are hypointensein the T1-weighted and hyperintense in the T2-weighted images,enhance strongly with contrast administration, and are mildlyto moderately vascular. Some cases may give cystic degeneration.Finally, meningiomas preserve the architecture of the foramen,present with a "dural tail," are hypo/isointense on the T1-weightedand hyperintense in the T2-weighted images, enhance uniformlywith contrast administration, and exhibit mild to moderate vascularity.4
Our patient underwent further evaluation. MRI of the brain revealedextension of the tumor, measuring 3.4 x 2.4 x 2.4 cm, to thepetrous apex, mastoid air cells, and superior cerebellopontineangle. The tumor surrounded the right internal carotid artery.There was also extension of the mass through the skull basewithin the right internal jugular vein and the hypoglossal canal(figure 2). CT angiography of the brain demonstrated right glomustumor (jugulotympanicum) with involvement of the middle ear,otic capsule, hypoglossal canal, jugular foramen, encasementof right ICA, and invasion of right sigmoid sinus and upperjugular vein (figure 3). Biochemical screening for catecholamineswas within normal limits.
Figure 3 CT angiogram of the head and neck showing right glomus tumor (jugulotympanicum) with involvement of the middle ear, otic capsule, hypoglossal canal, jugular foramen, encasement of right ICA, and invasion of right sigmoid sinus and upper jugular vein
Question for consideration:
What was the cause of the patient’s syncopal episodesand of her subsequent vertigo?
Syncope is not commonly reported as a manifestation of glomustumor. Its etiology should be sought in the baroreflex failure.Baroreflexes originate in the great vessels of the neck andthorax and prevent arterial pressure from fluctuating excessively.Information about distention of the vessel wall is transmittedfrom baroreceptors in each carotid sinus via the glossopharyngealnerves and in the aortic arch via the vagus nerves. The brainstemstructures receiving the information are the commissural, dorsolateral,and medial portions of the nucleus tractus solitarii. The vagusnerves are the efferent pathway of the reflex. Abnormalitiesin the baroreceptors, the IX or X nerves, or the brainstem couldlead to baroreflex failure.5 A few cases of paragangliomas leadingto blood pressure dysregulation6 and to syncope7 have been reportedin the literature. The postsyncopal vertigo was likely peripheral,possibly due to impairment in the microcirculation of the labyrinth.A plausible explanation is that the patient had compensatedvestibulopathy (i.e., the affected side had no vestibular responses)and the syncope reduced the microcirculation to the contralateralfunctional vestibular system, resulting in imbalance and vertigo.
Question for consideration:
What is the natural history of the disease and what are themanagement options for this patient?
Paragangliomas are slow-growing, mostly benign tumors. Radiationand observation are palliative and surgery is curative. A treatmentplan should be individualized based on the diagnostic tests,the tumor type, and the patient age and health.8
This patient had an MRI and CT scan that showed encasement ofthe right internal carotid artery. There was extensive discussionwith the patient regarding the best course of action. Curativetreatment with surgery would entail a combined otologic-neurosurgicalapproach with sacrifice of the internal carotid artery and thecranial nerves VII, VIII, IX, X, XI, and XII. The resectionof the internal carotid would have to be done at the level ofthe circle of Willis with preoperative test occlusion. Thissurgical approach could put the patient at high risk for postoperativestroke. It was felt that radiation therapy, alternatively, mightresult in poor wound healing and risk of persistent CSF leakand meningitis. Given her high functional level, the patientelected not to pursue any treatment.
Paragangliomas are slowly growing hypervascular tumors arisingfrom a neural crest progenitor cell. Paragangliomas can be dividedinto the adrenal and the extra-adrenal system. The latter canbe further subdivided into the branchiomeric (carotid, jugulotympanic,subclavian, laryngeal, coronary, aorticopulmonary, and orbitalparaganglia), the intravagal, and the aorticosympathetic paraganglia.The last are often chromaffin positive and secrete catecholamines.9
The most frequent paragangliomas above the neck are carotidbody tumors followed by glomus jugulare tumors. Although mostlybenign, their critical location next to important neurovascularstructures renders these tumors clinically aggressive. Mostof these tumors will manifest with a palpable neck mass, tinnitus,pulsatile mass in the ear, and various lower cranial nerve palsies.10
Only a small proportion (<10%) of head and neck paragangliomasis hyperfunctional. The combined sensitivity for all three catecholaminesin identifying hypersecreting extra-adrenal paragangliomas hasbeen reported close to 90%.11 However, it is important to recognizethese cases preoperatively to allow adequate pharmacologic preparationbefore anesthesia and surgery.
Extra-adrenal paragangliomas can be solitary or multicentricand can arise sporadically or in familial patterns. Only 6%of jugulotympanic paragangliomas metastasize. Previous studieshave emphasized the significance of identifying immunohistologicallytwo distinct cell populations, the chief cells (type I) andthe sustentacular cells (type II). The latter are typicallyabsent in aggressively metastasizing paragangliomas.9
Most head and neck paragangliomas exhibit a slowly progressivecourse. Surgery is the definitive therapeutic modality. Radiotherapyis indicated for older patients, those at risk for surgery,and extensive tumors in order to stabilize the tumor, improvethe symptoms, and decrease morbidity.12 Embolotherapy must bebasically preoperative and is not curative.13 Approximatelyone third of patients have persistent or recurrent disease andlong-term follow-up is necessary.11
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