The amyloidoses are heterogeneous disorders characterized by interstitial deposition of proteinaceous fibrils, arranged in cross-beta pleated sheets. Many diverse proteins are capable of undergoing conformational changes and polymerization to produce these fibrils; the fibrils are insoluble, resistant to proteolysis, and often cytotoxic.1 Monoclonal immunoglobulin (Ig) light chains produce the fibrils in primary amyloidosis, which comprises some 75% of amyloidosis cases seen at tertiary referral centers.1 Neuropathy occurs in approximately 15% of primary amyloidosis cases, typically manifesting as an axonal sensorimotor polyneuropathy, carpal tunnel syndrome, or both.1,2⇓ Certain familial amyloidoses, particularly type IV, commonly produce cranial neuropathies,1 but multiple cranial neuropathies are uncommon in primary amyloidosis.1-3⇓⇓ We report a patient in whom primary amyloidosis presented with intractable epistaxis and multiple cranial neuropathies.
Case report.
A 59-year-old right-handed woman had first developed recurrent, unexplained epistaxis about 7 years previously. Over the next 2 years, she additionally experienced persistent nasal congestion, rhinorrhea, and “internal facial pressure.” Chin “numbness” also began, followed the next year by progressive, perioral hypesthesia and bilateral lower extremity paresthesias. Two years ago, intermittent horizontal diplopia occurred, as did progressive left ptosis, hyposmia, dysgeusia, and xerostomia, and she underwent sinus surgery for intractable epistaxis. Histologic examination of the ethmoid sinus mucosa revealed amyloid deposition with positive staining for Congo red, as well as kappa and lambda light chains. She was referred to our institution for further evaluation and treatment.
On physical examination she had left ptosis; severe, bilateral ophthalmoparesis; bilateral nasal telangiectasias; partial bilateral seventh nerve palsies; anesthesia to pinprick in a “muzzle distribution,” although corneal reflexes were preserved; and limb hyporeflexia throughout with bilateral loss of vibration greater than pinprick in the legs. Hepatomegaly was absent. Serum immunoelectrophoresis revealed an IgM kappa monoclonal protein, with an M peak of 1.31 g/dL. Free kappa light chains were found in the urine and the total urinary protein was 336 mg/24 hours (normal, 27 to 93 mg/24 hours). Other serum and urine tests, including liver function tests, were unremarkable. Amyloid deposits were present in the bone marrow, but not in subcutaneous fat. The CSF protein was mildly elevated (74 mg/dL), but other CSF studies were normal, as were chest radiographs, an electrocardiogram, and an echocardiogram. EMG and nerve conduction studies demonstrated bilateral, chronic, active facial and trigeminal neuropathies, as well as a polyradiculoneuropathy of the lower extremities. A postcontrast, fat-suppressed cranial MRI revealed thickening and prominent gadolinium enhancement along all three divisions of both trigeminal nerves (figure). Other cranial nerves did not enhance, nor did the meninges. The multiple cranial neuropathies, polyradiculoneuropathy, and nasopharyngitis were attributed to primary amyloidosis. Given the lack of visceral amyloidosis involvement, chemotherapy was not initiated. Eighteen months after diagnosis, the patient remains free of cardiac, pulmonary, hepatic, or renal dysfunction. She has more diffuse facial numbness and complete left-sided ptosis, and uses a cane to walk. One of the patient’s home physicians initiated a trial of oral prednisone, starting at 40 mg, which was tapered off over 8 weeks, but she did not improve symptomatically.
Figure. This fat-suppressed, postcontrast, coronal T1-weighted image reveals bilateral enhancement and thickening of the third divisions of the trigeminal nerve as they descend through the foramen ovale (arrows).
Discussion.
Amyloidosis involvement of the nasopharynx and paranasal sinuses is rare. Less than 10 cases have been reported and none was associated with concomitant cranial neuropathies.4 When amyloidosis affects cranial nerves, it usually also produces significant nephropathy, which can be a clue to the diagnosis.2,5⇓ Our patient’s renal function was normal, however, and there was no evidence of cardiac or hepatic disease, both of which are common sequelae of amyloidosis.5 Nonetheless, the pattern of trigeminal nerve enhancement on our patient’s postcontrast, fat-suppressed cranial MRI (see the figure) is quite similar to MRI images of a facial nerve infiltrated by amyloid reported by Braganza et al.6 Although these striking imaging findings are not diagnostic of amyloidosis, they are associated in our patient with amyloid deposits in the nasopharyngeal mucosa and bone marrow, as well as a monoclonal IgM kappa protein in serum and urine. Her evaluation did not yield another plausible etiology of her cranial neuropathies and polyradiculoneuropathy. Thus, it is likely that amyloidosis produced this patient’s cranial neuropathies and polyradiculoneuropathy, as well as her chronic nasopharyngitis.
Amyloidosis is a rare cause of multiple cranial neuropathies.7 To our knowledge, this is the first report of a case of amyloidosis involving the nasopharynx and multiple cranial nerves.
Acknowledgments
Acknowledgment
The authors thank Dr. John Wald for his expert advice.
Footnotes
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Copyright © 2000 by AAN Enterprises, Inc.
- Received March 13, 2000.
- Accepted August 2, 2000.
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