Journal of Neuro-Ophthalmology, September 1988, Volume 8, Issue 3

Central bilateral sixth nerve palsy associated with a unilateral preganglionic Horner's syndrome.

Unilateral peripheral sixth nerve palsy associated with an ipsilateral postganglionic Horner's syndrome has previously been described. Isolated bilateral sixth nerve palsy due to a pontine hemorrhagic lesion, however, is a rare occurrence. We describe such a case whose only other neurological finding was a unilateral preganglionic Horner's syndrome.

/ourfUll ofCliniCilI Nturo-op!rlhalmology 8(3): 179-184.1988. 19 Raven Press, Ltd., lew York Central Bilateral Sixth Nerve Palsy Associated With a Unilateral Preganglionic Horner's Syndrome Rodney I. Kellen, M.B., B.ch., M.Med., F.R.C.S" Ronald M. Burde, M.D., Fred J, Hodges, III, M.D., and Gill Roper-HaU, D.B.O.T. Unilateral peripheral sixth nerve palsy associated with an ipsilateral postganglionic Horner's syndrome has previously been described. Isolated bilateral sixth nerve palsy due to a pontine hemorrhagic lesion. however, is a rare occurrence. We describe such a case whose only other neurological finding was a unilateral pregangli­onic Horner's syndrome. Key Words: Sixth nerve palsy-Horner's syndrome­Pons- Hemorrhage. From the Departments of Ophthalmology (R.l.K.. R.M.B., G.R.H.) and 'eurology and Neurological Surgery (R.M.B.), and the Mallinkcrodt Institut of Radiology (F.j.H.), Wash­ington University School of Medicine, SI. Louis, Missouri. Address correspondence and reprint requests to Dr. R. M. Burde, Deparlment of Ophthalmology, Montdiore Ho pita I and Medical Center, 111 East 210th Street, Bronx, NY 10467, U.S.A. 179 Isolated abducens (sixth) cranial nerve palsy, whether unilateral or bilateral, is usually due to an affection of the peripheral portion of the nerve, distal to its exit from the base of the pons. There is no localizing value attached to an isolated sixth nerve palsy (1). The nucleu of the abducens nerve in the dorsal pons is, in reality, a secondary gaze center containing two populations of cells (2). One group of cells forms the abducens nerve while the other group of cells are intemeurons that join the contralateral medial longitudinal fasciculus (MLF) and synapse in the medial rectus subnucleus of the oculomotor nerve nucleus. Lesions affecting the sixth nerve nucleus, therefore, cause gaze pal iI'S and not isolated abducens pal ies (3). When the intra pontine fascicular portion of the sixth nerve i damaged, other neur logical deficits may occur, e.g., contralateral hemiplegia (Millard­Gubler syndrome) or ipsilateral facial paresis with facial analge ia (Foville syndrome) (1). We de­scribe a patient with bilateral sixth nerve pal yas­sociated with a preganglionic Homer's syndrome on one side due to a small intrapontine hemor­rhage. CASE REPORT A 66-year-old right-handed white man with a history of hypertension, stable angina, hypercho­lesterolemia, and hyperuricemia was in his usual state of health 3 weeks prior to consultation. Then, when he awoke on ovember 7, 1986, he noted binocular horizontal diplopia and was seen at an­other hospital where the diagnosis of a left sixth nerve palsy was made. Two weeks later, he noted that the separation of the two images was notice­ably larger. He had no associated headache, tin- 180 R. 1. KELLEN ET AL. nitus, or other neurological symptoms. At no stage did he lose consciousness. His medications included spironolactone, hydrochlorothiazide, metoproloL isosorbide dinitrate, nitroglycerin, al­lopurinol, and gemfibrozil. He consumed one or two beers per week. The rest of his history was unremarkable. When we saw him for the first time he was alert, cooperative, and normotensive. Bilateral xanthe­lasmas were present. The afferent visual system was normal. The left pupil was smaller than the right by 1 mm, and a left ptosis of I mm was also present. Levator function was equal. There was no anhidrosis. The left pupil failed to dilate to 5% co­caine but did dilate with 1% hydroxyampheta­mine, indicating a preganglionic left Horner's syn­drome (4). The patient had blue irides, and his right pupil dilated with 5% cocaine. Slit-lamp bio­microscopy demonstrated bilateral arcus senilis. Funduscopy and kinetic visual fields were normal. Ocular motility examination was remarkable for a 35 prism diopter esotropia in primary position at distance. The angle increased to 45 prism diopters in right and left gaze. At near, 30 prism diopters of esotropia was measured (an accommodative target was used). either eye could abduct beyond the midline when ductions and version were tested. Oculovestibular reflexes also failed to produce ab­duction past the midline. A Hess screen confirmed bilateral abduction failure with overaction of the medial rectus muscles in each eye (Fig. 1). Con­vergence, tested unilaterally, was normal. Vertical eye movements were normal. Forced duction and Tensilon tests were both negative. Corneal sensation was present and equal in both eyes. Except for mild conduction deafness on the right, all the cranial nerves, including five and seven, were intact. The peripheral nervous system and the cerebellar system were normal. A hemogram and a lipogram were normal. Serum electrolytes were remarkable for serum cal­cium of 10.21100 ml (normal, 8.9-10.3) and serum phosphate of 3.6 mg/100 ml (normal 2.5-4.5). A lumbar puncture showed a normal cerebrospinal fluid pressure, chemistry, and cytology. Serologic testing for syphilis was negative in both blood and cerebrospinal fluid. The initial computerized tomography (CT) scan demonstrated a I-cm density directly ventral to the floor of the fourth ventricle, which underwent slight or questionable enhancement after i. v. con­trast injection (Fig. 2). Magnetic resonance imaging (MRI) 1 month later showed the lesion to have increased signal on TI, proton density, and T2-weighted images (Fig. 3). The CT and MRI re­sults within this time sequence and at this location were virtually pathognomonic of acute and sub­acute hemorrhage, respectively (5). The patient was closely observed over the en­suing 6 months. During this time, there was a re­duction in the esotropia and improvement in lat­eral rectus function in both eyes, confirmed with a Hess chart (Fig. 4). An MRI scan 5 months after the first one dis­closed that the elevated signals had become hy­pointense with respect to brain (Fig. 5), findings • ' < ;v.wing bilateral abduction deficits with associated medial rectus overaction. FIG. 2. CT examination before (A) and after (8) injection disclosed a density in the pons just below the floor of the fourth ventricle (arrow). There is questionable or slight enhancement following contrast injection. FIG. 3. MRI 1 month later. Sagittal Tl (A), axial proton density (8), and axial T2 (C) images all show a markedly elevated signal in the pons. Tiny low and isodense signals are contained within it. The ele­vated signal is characteristic of subacute hematoma composed of hemoglobin breakdown products (deoxyhemoglobin and methemoglobin). ttl"'''. -1-+--+- fY'~~""'-+-H-_ FIG. 4. The follow-up Hess chart 6 months after the onset of symptoms showing improvement of lateral rectus function in both eyes. FIG. 5. MRI 5 months after the first ex­amination. Sagittal T1 (A), axial proton density (8), and axial T2 (C) images now show markedly decreased signal in the pons, still containing tiny isointense features. The decreased signal is pri­marily due to the paramagnetic effect of phagocytized hemosiderin and prob­ably some calcium deposition. CENTRAL BILATERAL SIXTH NERVE PALSY 183 that suggest calcification and/or phagocytized he­mosiderin resulting from breakdown of hemo­globin (1,6). Both of these are known to occur in cavernous hemangiomata that have bled overtly or occultly. A CT scan (without contrast) approxi­mately 1 year after the initial clinical event showed a sightly smaller density in the same location, without mass effect (Fig. 6). This was interpreted as diffuse calcification within the tiny lesion. The uncertain initial enhancement is a common finding in cavernous angiomas either partially cal­cified or with acute hematoma, but neoplasm was a necessary consideration (7). Subsequently, how­ever, an underlying neoplasm became extremely unlikely in the absence of initial or final mass ef­feet and without a final elevated MRI signal. The tiny features within the lesion on the MRI scan were consistent with tiny patent vessels and glial and fibrous structures. These are surrounded by and mixed with calcium, which produces the in­creased density on CT, and phagocytized hemo­siderin, which markedly reduces the MRI signal. DISCUSSION Acute pontine vascular lesions, due either to hemorrhage or infarction, are usually associated with devastating neurological sequelae (8,9). The reason for this is fairly obvious when one con­siders the tightly packed, complex neurocircuitry in this region. The average adult human pons measures about 25 x 33 mm (10). Pontine hemor- FIG. 6. CT without contrast injection approximately 10 months after the initial hemorrhage shows de­creased size of the lesion in the pons but continued or new density, indicating the existence of fine calcifica­tion. rhages usually begin at the junction of the teg­mentum and base and expand rapidly to form a round or oval hematoma, destroying the center of the pons. The accompanying signs include qua­draparesis, coma, and rapid irregular respirations. All horizontal eye movements are abolished, and the pupils are small but reactive. Ocular bobbing may also be noted. If the hematoma develops more slowly, then the early findings may be asym­metrical and may include deafness, dysarthria, fa­cial numbness, and asymmetrical facial and limb weakness. Coma usually follows. Large pontine hemorrhages are invariably fatal, death occurring 24-48 h after the onset. The sixth nerve nucleus is in reality a gaze center (2,3,11-13) containing cells for direct lateral rectus stimulation as well as interneurons who!'e axons run in the contralateral medial longitudinai fasciculus to innervate the contralateral medial rectus subnucleus of the oculomotor nucleus. Therefore, a lesion of the sixth nerve nucleus will result in a gaze palsy and not an isolated sixth nerve palsy. A pontine lesion causing only an ab­duction deficit must therefore be affecting the sixth nerve fascicle alone as it runs ventrally through the pontine reticular formation. Both sixth nerve fascicles are initially close to the mid­line in the caudal pons as they leave their respec­tive nuclei. It is possible to postulate a bilateral in­terruption of pathways from the horizontal gaze center to the large motor nuclei of the sixth nerve, i.e., a supranuclear lesion of a sort. The failure of oculovestibular input that bypasses the horizontal gaze center to overcome the abduction deficit ob­viates this possibility. In a series of bilateral sixth nerve palsies, Keane (14) had six cases of brain stem infarction, but he did not describe whether there were other neuro­logical accompaniments. Rucker's extensive series of oculomotor nerve pareses (15) did not distin­guish unilateral from bilateral cases, nor did he describe any cases of isolated pontine hemor­rhages. The precise location of the pupillodilator fibers of the sympathetic system in the brain stem is not yet defined in humans. From clinical material and animal experiments, two pathways are postulated (16,17). The descending stimulating pathway is lo­cated in the ventrolateral region associated with the spinothalamic tract. Associated with these fibers is a collection of ascending axons thought to be inhibitory to the Edinger-Westphal nucleus. These fibers may be related to the pupillary dilata­tion, which occurs as a result of painful or noxious stimuli. There is a second group of inhibitory as- J Clill Nf14ro-oplJthnllllol. Vol. 8. No.3. 1988 184 R. I. KELLEN ET AL. cending fibers lying on either side of the midline in the pons. It is these fibers that may have been injured in our patient. Recently, peripheral unilat­eral sixth nerve palsies have been associated with postganglionic Horner's syndrome (18) due to the close relationship of the oculosympathetic fibers with the sixth cranial nerve in the cavernous sinus as described by Parkinson (19). Our case may re­flect a centrally located close anatomical relation­ship between the sixth cranial nerve and the ocu­losympathetic pathway. Isolated central bilateral sixth nerve palsy to­gether with a unilateral central oculosympathetic paresis due to pontine hemorrhage, to the best of our knowledge, has not been previously de­scribed. MRI afforded us the opportunity to visu­alize the location of the hemorrhage in vivo and to postulate that both sixth nerve fascicles were in­jured as was an ascending inhibitory pathway of the oculosympathetic system on one side. Acknowledgment: Supported in part by an unre­stricted grant from Research to Prevent Blindness, Inc., New York (Department of Ophthalmology). REFERENCES L Glaser JS. In: Duane TD, Jaeger EA, eds. Clinical ophthal­molofS'J. vol. V. Philadelphia: Harper & Row, 1986:Chaps 2-8. 2. Baker R. Highstein SM. Physiological identification of in­terneurons and motoneuron in the abducens nucleus. Bruhl Res 1975;94:292-8. 3. Meienberg 0, Buttner-Ennerver JA, Kraus-Ruppert R. Uni­lateral paralysis of conjugate gaze due to lesion of the ab­ducens nucleus. Chnico-pathological case report. NellTt}· ophthalmology 1981;2:47-52. 4. Smith PG, Dyches TJ, BurdI' RM. Topographic analysis of Horner's syndrome Otolaryngol Head Neck 5urg 1986;94:451-7. 5. 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