Cranial Polyneuropathies in Multiple Sclerosis: Case Report and Literature Review

Richard W. Thomas, MD, DDS, Department of Otolaryngology-Head and Neck Surgery, Madigan Army Medical Center, Tacoma, Washington; Douglas A. Liening, MD, Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Washington, DC; Andrew E. Auber, MD, Department of Radiology, Brooke Army Medical Center, San Antonio, Texas; Robert E. Johnson, MD, Department of Otolaryngology-Head and Neck Surgery, Tripler Army Medical Center, Honolulu, Hawaii.

Although cranial neuropathies are common disorders in multiple sclerosis patients, multiple cranial nerve involvement is an unusual occurrence. Correlation of clinical symptoms with magnetic resonance imaging evidence of demyelinating central nervous system lesions can confirm the diagnosis. The authors report on the case of a 43-year-old woman who initially was thought to have suffered a brainstem infarct but, in fact, had developed multiple cranial nerve functional deficits. Treatment of multiple sclerosis remains primarily supportive in nature, with corticosteroids used for acute exacerbations and chronic progression. [Ear, Nose & Throat Journal 78(2):118-121, 1999. © 1999 MEDQUEST Communications, LLC]

Multiple sclerosis (MS) is a chronic neurologic disease with significant variability in clinical severity and expression.[1-3] Although the development of cranial neuropathies in MS patients is a common finding, these disorders tend to appear later in the course of the disease and rarely have been reported to involve multiple cranial nerves.
We present an unusual case of multiple cranial nerve functional deficits in a patient who initially was presumed to have suffered a brainstem infarct. Magnetic resonance imaging (MRI) revealed a multiplicity of lesions with a waxing-and-waning appearance on serial studies. These findings and supportive laboratory data were most consistent with a demyelinating disease process and the diagnosis of MS was made.

Case Report
A 43-year-old woman came to the emergency department complaining of new onset diplopia, mild dysphagia, right-side decreased hearing acuity and muscular weakness. The patient first noted these symptoms two days before the day of admission. She denied any vertigo, paresthesias or recent viral symptoms.
Physical examination revealed a well-developed white woman who was afebrile, had stable vital signs and was in no apparent distress. The neurologic examination was significant for horizontal nystagmus of the left eye. A right lateral rectus muscle palsy was noted as well as a sluggish pupillary reflex. The left pupil was normally reactive.
The patient had complete right lower motor neuron distribution facial paralysis and right facial paresthesia in the distribution of all divisions of the fifth cranial nerve. Additionally, she had decreased hearing acuity and loss of the gag reflex on the right, with tongue deviation to that side on protrusion. Hypopharyngeal inspection revealed normal true vocal cord mobility with no evidence of masses or lesions. The remainder of the head and neck examination was unremarkable.
A mild paresis of the right upper extremity and weakness with diminished vibratory sensation in the right lower extremity were demonstrated. Her deep tendon reflexes were brisk throughout, and no additional focal deficits were noted on neurologic exam.
The patient was taking warfarin sodium (Coumadin) for a history of two episodes of deep vein thrombophlebitis. No other significant previous health conditions were identified, and she was admitted to the neurology service with a working diagnosis of brainstem ischemia. Computed tomography (CT) revealed no evidence of hemorrhage or optic nerve impingement. MRI showed a poorly circumscribed right middle cerebellar peduncle lesion that failed to enhance with gadolinium contrast (Figure 1). Cerebrospinal fluid tested negative for oligoclonal antibodies, and the myelin basic protein level was marginally positive at 7.4 ng/ml. Based on these findings, the differential diagnoses included infarction, tumor or demyelinating processes. Supportive care was provided, and her physical condition gradually improved with near-total resolution of her symptoms. On hospital day 10, just before transfer to a rehabilitation facility, her status acutely deteriorated. Physical examination revealed a unilateral palsy of cranial nerves V through XII.
art-ent7802.04.fig1.JPEGart-ent7802.04.fig1.JPEG Figure 1. (click image to zoom) Axial spin-echo T2-weighted image at the level of the pons obtained on the day of hospital admission. The image shows subtle mass effect and poorly circumscribed, heterogenous increased T2 signal intensity in the medial aspect of the right middle cerebellar peduncle (large arrowhead). A smaller central area of homogenous increased signal is seen (small arrowhead).

MRI demonstrated interval enlargement of the right middle cerebellar peduncle lesion with an area of increased attenuation in the occipital horn of the right ventricle (Figure 2). There was enhanced signal in the occipital pole periventricular region, with evidence of a mass effect (Figure 3). Repeat lumbar puncture revealed oligoclonal bands and moderate elevation of the myelin basic protein level to 11 ng/ml.
art-ent7802.04.fig2.JPEGart-ent7802.04.fig2.JPEG Figure 2. (click image to zoom) Axial spin-echo proton-density T2-weighted image obtained on day 9 showing a subtle asymmetric increase in the signal of the right occipital horn ependyma/subependyma (small arrowheads).

art-ent7802.04.fig3.JPEGart-ent7802.04.fig3.JPEG Figure 3. (click image to zoom) Axial post-gadolinium spin-echo T1-weighted image shows marked enhancement of this lesion (arrowhead) and asymmetric narrowing of the right occipital horn due to associated mass effect.

The clinical, laboratory and serial MRI evidence was consistent with MS. Anticoagulation medication was discontinued and high-dose methylprednisolone therapy initiated. A tracheostomy and a feeding gastrostomy tube were required. With aggressive daily occupational and physical therapy, the patient demonstrated significant clinical recovery over the next few days. A final MRI obtained on hospital day 20 revealed a decreased T2 signal and contrast enhancement compared with earlier studies (Figure 4).
art-ent7802.04.fig4.JPEGart-ent7802.04.fig4.JPEG Figure 4. (click image to zoom) Axial T2-weighted image obtained at the level of the pons (compare to Figure 1) on day 20. The image demonstrates interval circumferential increased size of the cerebellar peduncle lesion, which now involves the facial colliculus medially (large arrowhead). The previously noted central necrotic area is smaller, apparently due to decompression into the fourth ventricle (small arrowhead).

The remaining four weeks of hospitalization were uneventful; the patient continued to show progressive recovery of neurologic functions. Her visual symptoms and paresthesias had resolved. The facial nerve examination result was consistent with a House-Brackmann grade III paralysis, and the hypoglossal nerve paresis was unchanged.
Audiologic evaluation confirmed normal bilateral hearing acuity, and the patient's gag reflex and speech articulation were significantly improved. Ambulating with the assistance of a walker, she was moved to a rehabilitation facility. One year after discharge, the patient had persistent, mild right facial paresis with continued decreased right hypoglossal nerve function manifested by moderate tongue hemiatrophy. The remaining neurologic functions had objectively and subjectively improved, and the patient almost had attained her prehospitalization activity level. To date, she continues physical and occupational therapy and has had no recurrent exacerbations.

MS is the most common demyelinating disease of the central nervous system (CNS). Usually affecting younger patients, MS is characterized by exacerbations and remissions. Although the exact etiology remains unknown, various environmental factors are likely to be involved in the pathogenesis.[1-3]
Since Charcot's original description,[4] the diagnosis has been primarily a clinical determination made in conjunction with laboratory test results. The advent of magnetic resonance imaging permitted the demonstration of lesions within the white matter of the CNS, which correlated with various clinical symptoms seen in affected patients.[5-7] Major advantages of MRI when compared with clinical monitoring are the ability to detect a significant amount of subclinical disease activity and the ability to monitor the efficacy of MS therapy by detecting active lesions.[5,6]
Although MS remains a common disorder primarily affecting the CNS myelin, studies have confirmed the existence of peripheral nervous system myelin deficits.[7,8] Whereas cranial nerve impairments may be manifest in this disease, extensive cranial polyneuropathies are rare occurrences. A review of the medical literature revealed no reports of profound, acute neurologic deficits involving multiple cranial nerves in a single patient.
In this case, the initial MRI examination demonstrated a poorly circumscribed middle cerebellar peduncle lesion that did not enhance with gadolinium contrast (Figure 1). Based on this appearance and location, the differential diagnosis included infarction, a demyelinating neurologic disease or a tumor, such as astrocytoma or glioblastoma multiforme.
Serial MRI evaluations demonstrated a minimal increase in mass effect over a three-week period. The degree of mass effect was less than what would be expected for a neoplastic lesion of this size (Figure 4). An infarct would likely have revealed a volume loss in the span of three weeks. This lesion location did not conform to an arterial vascular territory, which made the diagnosis of infarction improbable. Furthermore, the rapid clinical deterioration seen in this case was not characteristic of a neoplasm.
The MR images obtained on hospital day 9 revealed a markedly abnormal T2 signal and contrast enhancement that was not previously evident (Figures 2, 3). Subsequent images indicated a paucity of these findings. The subarachnoid spread of a neoplastic process, such as glioblastoma multiforme, would not be expected to dissipate as in this case. These lesions, with periventricular involvement and waxing-and-waning appearance on serial exams are most consistent with the diagnosis of a demyelinating disease process.
Demyelinating foci, or plaques, are considered to be the causative factors responsible for the symptoms and findings of MS. Periventricular foci involving the lateral fourth ventricle are common, and plaques may be present in the spinal cord, midbrain, pons and basal ganglia. Brainstem abnormalities are demonstrated in approximately 15% of patients with clinical symptoms.[9]
Whereas bulbar lesions can cause faulty deglutition and speech, cerebellar lesions may result in ataxia, nystagmus, dysarthria or impaired lower extremity proprioception. McAlpine et al[2] reported the presence of nystagmus in up to 70% of patients in his series.
Although usually horizontal in nature, vertical nystagmus is evident in a significant percentage of persons suffering from MS. The literature contains numerous reports of cranial neuropathies in MS patients. Visual complaints are most common, and abducens nerve dysfunction manifested by diplopia may be a presenting symptom. Acute third nerve palsy with pupillary involvement also has been cited as a presenting sign of MS.[7-10] Various sensory signs and symptoms are frequently found in affected individuals. Paresthesias of a portion of the trigeminal nerve distribution are fairly common, whereas motor root involvement is considered to be a relatively rare occurrence.[8,11]
Seventh cranial nerve palsies in MS patients have a reported incidence of 15%. Facial motor function abnormalities were similarly reported by Muller[12] and Grenman.[13] The basis for treatment of MS remains general supportive care. Corticosteroids are useful for acute relapses and for treating chronic progression of the disease.[14] Additional immunosuppressive agents including cyclophosphamide (Cytoxan), azathioprine (Imuran) and interferon beta-1b have been used in various clinical studies. Interferon 1-a, a recombinant form of human interferon beta, recently has been approved by the U.S. Food and Drug Administration for the treatment of patients experiencing relapsing forms of MS.[15] The exact mechanism of action of these agents in treating MS remains unclear.