Bilateral Internuclear Ophthalmoplegia

Bilateral Internuclear Ophthalmoplegia; Pendular Horizontal Oscillations; Lid Nystagmus; Upbeat NystagmusBlurred vision OscillopsiaThis patient was seen at the Yale Eye Center at the age of 37. She had a long history of multiple sclerosis. At age 22, she had an acute attack of optic neuritis in the left eye which recovered fully within three weeks. Some months later she had a recurrent episode in the same eye, which also recovered fully. At age 26, her third attack of MS, was more severe with acute numbness of the left side of the body from the waist down and involving the leg. On exertion and when exposed to heat the left leg became weak and she had difficulty walking. (positive Uhthoff's sign). On this occasion however her signs and symptoms did not remit and over the next few years her deficits gradually progressed until by 1989 she was wheelchair bound. In that year, she was admitted to the Mass General Hospital for evaluation and was found to be very depressed, owing to having to leave her job as a proof reader because of disturbing oscillopsia and blurring of vision. Neuro-ophthalmological examination: Visual acuity (VA): 20/200 OU Reads J2 OD, J4 OS. She was unable to insert her contact lenses owing to marked ataxia of the upper extremities and impaired dexterous movements of the hands. Ocular motility: • Paresis of adduction of the right eye on gaze left • Abducting nystagmus of the left eye on gaze left • Paresis of adduction of the left eye on gaze right • Abducting nystagmus of the right eye on gaze right • Normal convergence • Full vertical gaze • Pendular horizontal oscillations • Intermittent primary position upbeat nystagmus Spinal tap: Eight years and 15 years after the onset of progressive relapsing MS, the cerebrospinal fluid showed an elevation of the protein (60-75mg/dl), an increase in the number of white blood cells (11-15), and elevated IgG with positive oligoclonal bands. Brain MRI: The brain MRI, with T1 and T2 weighted images in the axial and sagittal view showed considerable periventricular bright signals in the T2 WI scans involving the frontal and occipital lobes. The bright signals were greatest in the occipital lobe. A small punctate hyperintense signal was present in the white matter in the posterior limb of the internal capsule on the left side. Several other small punctate hyperintense signals were present in the centrum semiovale bilaterally. Electronystagmogram: 1. Spontaneous and gaze nystagmus - Irregular horizontal eye movement with eyes open and eyes closed. On right lateral gaze with eyes open nystagmus present in the right eye, fast phase to the right. 2. Optokinetic nystagmus (OKN) - Horizontal OKN was attempted with a sinusoidal full field strimulus. No nystagmus was provoked. Down beating OKN provoked with an up moving stimulus. No upbeating nystagmus provoked with down moving stimulus. Impression: Left internuclear ophthalmoplegia (INO) and saccadic breakdown of visual-vestibular interaction consistent with a cerebellar or brainstem lesion because of rotation induced nystagmus and absent optokinetic nystagmus. Oscillopsia, an illusion of movement of the visual world, was the major visual disability in this patient. She was seen in the Low Vision Aid Clinic to see if optical devices could stabilize the retinal image. a) High plus lenses combined with a high minus contact lens (Rushton and Cox, 1987, JNNP Vol 50, 411-415) b) Base out prisms to induce convergence with minus lenses to correct accommodation (as used in congenital nystagmus by (Dickenson Physiological Optics 1986). Prism therapy failed to stabilize her vision. Drug therapy with three different medications, baclofen, meclazine and cogentin was also unsuccessful and because conservative measures failed she was referred for consideration of Botulinum toxin therapy. Botulinium Toxin In 1991 the use of botulinum toxin (botox) to suppress involuntary eye movements had not been well studied. Halgerson reported getting beneficial effects in some patients with nystagmus using intraorbital injections into the eye muscles. At that time no large medical studies were available. The patient was, however, anxious to be treated in an effort to improve her vision to watch TV and, after being fully informed of all the risks and possible complications, she agreed to a trial of botox. The procedure plan was to obtain pre-injection video tapes of her eye movements and then inject botox into the extraocular muscles of the right eye under EMG control. Since her oscillopsia was due to acquired pendular horizontal oscillations, the goal was to dampen and hopefully stop the oscillations by injecting botox into the lateral and medical recti of the right eye. The risk of injecting botox only into these two muscles was the possibility that it would cause diplopia, and that diplopia might be more problematic to her than oscillopsia. The procedure went ahead as planned and the dose of botox into the medial rectus and lateral rectus muscles was sufficient to cause substantial dampening of the horizontal pendular oscillations, but they were not completely stopped. Immediately following, the patient had partial ptosis and diplopia but nevertheless was pleased with the result and she was willing to patch the left eye to prevent diplopia to watch TV. Four weeks after the injection her visual acuity in the right eye had improved to 20/70, and in the uninjected left eye it remained at 20/200. The future botox treatment plan was to let the botox effect of the first set of injections wear off over three months and then reexamine her. At that time, a new injection strategy was to be planned to eliminate toxin spread to the levator palpebra superioris muscle and prevent the development of ptosis. Unfortunately, she was lost to follow up.This patient had a bilateral INO with • Paresis of adduction of the right eye on gaze left • Abducting nystagmus of the left eye on gaze left • Paresis of adduction of the left eye on gaze right • Abducting nystagmus of the abducting right eye on gaze right. • Normal convergence • Full vertical up and downgaze and • Pendular horizontal oscillations of relatively high frequency that appeared to dampen after a blink. When she maintained fixation for a short time without blinking or making a saccades, the oscillations re-emerged. The oscillations were partially suppressed following a saccade and on convergence. • Intermittent primary position upbeat nystagmus was present. The Clinical Features of an INO are: 1. Medial rectus muscle weakness ipsilateral to the side of the lesion with paresis of adduction or adduction lag. 2. Abducting nystagmus of the eye contralateral to the lesion - Dissociated nystagmus 3. Normal convergence 4. Skew deviation - hypertropia on the side of the lesion 5. Dissociated vertical nystagmus - downbeat with greater torsional component in the contralateral eye Bilateral INO with bilateral lesions of the MLF may also have Gaze evoked vertical nystagmus Impaired vertical pursuit Decreased vertical vestibular response Small amplitude saccadic intrusions suggesting involvement of the brainstem adjacent to the MLF Weakness of adduction is due to impaired conduction in axons from the abducens internuclear neurons which project to the medial rectus motor neurons in the contralateral oculomotor (third nerve) nucleus. Adduction weakness is most evident during saccades and adduction lag is brought out clinically by asking the patient to look all the way to the right and all the way to the left (i.e. make large saccades) back and forth across the midline. The speed of the adducting eye depends on a strong agonist contraction. The adducting saccade may be slow and hypometric. In the abducting eye, abducting saccades are hypometric with centripetal drifts of the eye and slowing. A series of small saccades and drifts have the clinical appearance of abducting nystagmus - dissociated nystagmus. Dissociated nystagmus may be due to: 1. Impaired ability to inhibit the affected medial rectus or 2. Dissociated nystagmus reflects the brain's attempts to compensate for the adduction weakness. For further discussion review Leigh JR, Zee DS. Diagnosis and Central Disorders of Ocular Motility Chp 12 Pg620-627 In The Neurology of Eye Movements 4th Edition Oxford University Press, New York 2006. Skew deviation, commonly seen in unilateral INO, is due to interruption of central projections in the otolithic pathway ascending in the MLF to the midbrain. The higher eye (hypertrophic) is usually on the side of the MLF lesion. Interruption of pathways mediating the vertical vestibulo-ocular reflex (VOR) may cause downbeat nystagmus with a greater torsional component in the eye contralateral to a unilateral INO. Comment Dr. Zee (DZ), on review of the case, pointed out an important observation that some MS patients, as in this case, showed transient suppression of horizontal oscillations following a saccade. With regard to transient primary position upbeat nystagmus, DZ felt this was probably attributable to a lesion(s) in the region of the nucleus intercalatus and the nucleus of Roller suggesting that either of these structures may relay vertical eye position signals to the cerebellum. Systematic comparison of the oscillations prior to, and following a saccade, has demonstrated that the oscillations are phase-shifted (reset) and that larger saccades have a greater effect than small saccades. This observation led Leigh and Zee to hypothesize that the pendular oscillations in MS patients arise in the neural integrator for eye movements, and that large saccades affect the timing of the oscillations by "resetting" the integrator with the large pulse of neural activity. Other structures that may play a role are the nucleus prepositus hyperglossi and the medial vestibular nucleus which are important components of the neural intergrator. Box 10-10 Clinical Features of Acquired Pendular Nystagmus. Pg 506 (2) Oscillopsia, an illusion of movement of the visual world, is a common presenting symptom of INO. Horizontal oscillopsia usually occurs from either the adduction lag or the abducting nystagmus. Vertical oscillopsia occurs during head movements and is caused by a deficient vertical VOR or, as in this case, by pendular vertical oscillations.Neuroimaging studies were not available in this patient. Illustrative images in another MS case are shown here. Figure 1 MRI Axial FLAIR scan showing white matter foci of increased signal intensity surrounding cavitating areas characteristic of long-standing MS. Figure 2 MRI axial FLAIR scan of deep periventricular foci of increased signal intensity surrounding cavitating areas Figure 3 MRI sagittal FLAIR scan with classic calloseptal deep periventricular foci perpendicular to ventricle surface classic for Dawson fingers Courtesy of Anne Osborn, M.D. To view neuroimaging of the brain in MS go to PowerPoint Presentation "Brain MRI in Multiple Sclerosis" linked in the Get Media field above.The medial longitudinal fasciculus (MLF) is a major pathway in the brainstem extending from the pons to the midbrain. The MLF carries signals for the control of horizontal eye movements For horizontal gaze: 1. The MLF contains axons from the abducens internuclear neurons and carries signals for horizontal saccades, the vestibulo-ocular reflex (VOR), and smooth pursuit. 2. These axons project to the medial rectus motor neurons in the contralateral oculomotor (third nerve) nucleus. For vertical gaze: 1. The MLF contains axons from the rostral interstitial MLF (riMLF) which carry vertical saccadic signals. 2. The MLF also contains ascending axons from the vesitibular nuclei which carry signals for the vertical VOR, smooth pursuit, gaze holding and otolith-ocular reflex. 3. Axons project to the oculomotor and trochlear (fourth nerve) nuclei, as well as the Interstitial Nucleus of Cajal.Review (7)Table 12-3 Etiology of Internuclear Ophthalmoplegia pg 622 (5)Intraorbital botox injections1. Gordon RM, Bender MB. Visual phenomenon in lesions of the medial longitudinal fasciculus. Arch Neurol 1966;15:238-240. http://www.ncbi.nlm.nih.gov/pubmed/5912004 2. Gresty MA, Hess K, Leech J. Disorders of the vestibuloocular reflex producing oscillopsia and mechanisms compensating for loss of labyrinthine function. Brain 1977;100:693-716. http://www.ncbi.nlm.nih.gov/pubmed/305272 3. Hauser SL, Goodin DE. Multiple Sclerosis and other demyelinating diseases in Harrison's Principals of Internal Medicine, 16th Edition, Kasper DL et al eds. McGraw-Hill, New York, 2005. 4. Keane, JR. Internuclear Ophthalmoplegia: Unusual Causes in 114 of 410 Patients. Arch Neurol 2005, 62(5):714-717. http://www.ncbi.nlm.nih.gov/pubmed/15883257 5. Leigh JR, Zee DS. Diagnosis of Central Disorders of Ocular Motility. Chp 12 pg 598-718. In: The Neurology of Eye Movements, 4th Edition, Oxford University Press, New York 2006. 6. Muri RM, Meienberg O. The clinical spectrum of internuclear ophthalmoplegia in multiple sclerosis. Arch Neurol 1985, 42: 851-855. http://www.ncbi.nlm.nih.gov/pubmed/4026628 7. Strominger MB, Mincy EJ, Strominger AI, Strominger NL. Bilateral internuclear ophthalmoplegia with absence of convergence eye movements. Clinico-pathological correlations. J Clin Neuro-ophthalmol 1986,6:57-65. http://www.ncbi.nlm.nih.gov/pubmed/300955