Fisher's One and a Half Syndrome

Unilateral Internuclear Ophthalmoplegia; Unilateral Horizontal Gaze Palsy; Upbeat Nystagmus on Upgaze; Convergence NormalPowerPoint presentation: One and a Half Syndrome: http://library.med.utah.edu/NOVEL/Wray/PPT/One_and_Half_Syndrome.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical SchoolBlurred VisionThis 44 year old woman presented in 1973 with an acute attack of optic neuritis in the right eye that fully recovered after a course of ACTH therapy. In 1991, 18 years later, she developed unsteadiness of gait, "walking like a chicken", stiff legs that jerked spontaneously in bed at night, and numbness in the legs distal to the knees. The left leg was more affected than the right. She had urinary frequency, urgency and occasional incontinence. She denied any symptoms in the upper extremities. She had a negative L'Hermitte symptom. In hot weather her legs became weak and fatigue increased (Uhthoff's symptom). Past History: Negative for additional neurological symptoms Family History: Negative for CNS disease. Neuro-ophthalmological examination: Visual acuity OD: 20/25, OS: 20/20 Right afferent pupil defect Mild dyschromatopsia OD Fundus exam showed optic atrophy OD. Normal optic disc OS Ocular Motility A left horizontal gaze palsy with gaze evoked nystagmus A left internuclear ophthalmoplegia on gaze right with adduction weakness OS Abducting nystagmus OD Full vertical gaze Upbeat nystagmus on upgaze (ill sustained) Convergence normal Neurological examination: Titubation Spastic paraparesis, with spastic left foot drop Marked hyperreflexia, bilateral ankle clonus and extensor plantar responses. Ataxia on finger-nose and heel-knee-shin Broad base spastic ataxic gait. Spinal tap: Cerebrospinal fluid protein 51 mg/dl, sugar 66 mg/dl, 4 white blood cells, elevated IgG and positive oligoclonal bands. VDRL negative. Brain MRI: MRI of the brain with gadolinium showed multiple white matter lesions in the central and periventricular white matter. The largest of these lesions was approximately 9 mm in diameter and ring enhancing, reflecting the presence of both acute and chronic demyelinating lesions consistent with a diagnosis of MS. MRI study of the cervical spine showed cervical spondylosis with disc herniation at C5-6 and C6-7 lateralizing to the right and compressing the spinal cord. A neurosurgeon recommended conservative management. Diagnosis: Multiple Sclerosis (MS) Treatment: The patient received high dose intravenous methylprednisolone 1,000 mg in 1,000 cc of dextrose saline daily for 5 days, then tapered to a dose of 500 mg. in 500 cc of dextrose saline daily for 2 days. Only the patient's gait improved on treatment.This MS patient had Fisher's one-and-a-half Syndrome characterized by: • A left horizontal gaze palsy with gaze evoked nystagmus • A left internuclear ophthalmoplegia on gaze right with adduction weakness OS • Abducting nystagmus OD • Full vertical gaze • Upbeat nystagmus on upgaze (ill sustained) • Convergence normal The "One-and-a-Half" syndrome was first described by Fisher in 1967. The disorder is characterized by a lateral gaze palsy in one direction with an internuclear ophthalmoplegia (INO) in the other direction. In the complete form of the syndrome, the ipsilateral eye lies fixed at the midline for all lateral movements; the other eye can only abduct and exhibits horizontal jerk nystagmus in abduction. The syndrome is usually due to a unilateral lesion in the lower part of the dorsal pontine tegmentum, affecting the ipsilateral paramedian pontine reticular formation (PPRF), the abducens nucleus, and internuclear fibers of the ipsilateral medial longitudinal fasciculus (MLF). These internuclear fibers originate in the contralateral abducens nucleus and terminate in the ipsilateral medial rectus subnucleus of the third nerve nucleus. In 1983 Michael Wall, who was a Fellow of mine at that time, reviewed all the patients that I had seen with the one-and-a-half syndrome between 1968 and 1982. Films or video tapes of eye movements were available for review in 9 cases. In 12 of 20 patients, the lesion was on the right side. The patient's ranged in age from 16 to 78 years. Prior to our publication in Neurology there had been only 29 reported cases of the one-and-a-half syndrome in the literature: 6 proven and 6 probable infarctions, 8 hemorrhages (1 traumatic) 5 gliomas, 1 arteriovenous malformation, 1 metastatic melanoma and 2 patients with MS. We added a further 20 patients. (Table 1) Brainstem infarction was the most common cause in elderly adults (Patients 17 to 20 (Table 2)). Four patients were age 61 to 78 years mean, 70 years. Two of them had hypertension. Three patients presented with neurologic complaints and one with diplopia. MS was the most common cause in 14 young adults aged 18 to 52 years, (mean 32 years). Twelve had definite MS and 2 possible MS. (Table 1) In 4 patients the one-and-a-half syndrome represented the initial presentation of MS. Two of these patients complained first of diplopia and one of blurred vision. Only 7 of 14 MS patients had visual complaints as the major symptom. Nine had diplopia, 5 had blurred vision, 3 had oscillopsia, and 2 had difficulty looking to one side. (Table 2 and 3) Associated Ocular Motility signs: Gaze evoked upbeat nystagmus Skew deviation Horizontal ipsilateral gaze nystagmus Rotary component to horizontal ipsilateral gaze nystagmus Spontaneous nystagmus to the contralateral side Absent or impaired convergence Saccadic vertical pursuit Gaze evoked downbeat nystagmus Impaired upward gaze Exotropia Esotropia Orthotropic In 10 MS patients whose eye position was documented in straight ahead gaze, 4 had exotropia, 2 had an esotropia and 4 were orthotropic. (Table 4) Associated Neurological signs: The most common associated cranial nerve lesions were an ipsilateral trigeminal sensory loss and a peripheral-type facial palsy. Seven patients had impaired coordination of the limbs. Only one patient had no neurological abnormality other than the one-and-a-half syndrome. (Table 5) Ten of the fourteen MS patients had recovery of eye movements: Recovery was complete in eight patients between 4 and 16 weeks after onset, and partial recovery occurred in two other patients followed for 4 weeks and 9 weeks.No neuroimaging studies were available on this patient.The two constituents of the one-and-a-half syndrome (ipsilateral horizontal gaze palsy and INO) can be analyzed anatomically to provide the basis for topographic localization of the lesion at the bedside. Horizontal gaze palsy. There are four theoretical possibilities to account for the ipsilateral horizontal gaze palsy. It may be due to a single unilateral lesion affecting: 1. The ipsilateral paramedial pontine reticular formation (PPRF) only 2. The ipsilateral abducens nucleus alone 3. Both the ipsilateral paramedial pontine reticular formation (PPRF) and the abducens nucleus, or, when two lesions are involved 4. The motoneuron root fibers of the ipsilateral abducens nucleus to the lateral rectus and the contralateral medial longitudinal fasciculus (MLF). Paramedial pontine reticular formation. The medial portions of the nucleus reticularis magnocellularis (or nucleus centralis pontis oralis and caudalis) have been designated the "paramedian pontine reticular formation" (PPRF), rostral to the abducens nucleus. The region extends from the abducens nucleus in a rostral direction toward the brachium conjunctivum and trochlear nucleus. It has been defined functionally because there are no distinct histologic boundaries. But anatomically, Graybiel, Büttner-Ennever, and Grantyn et al all showed inputs from discrete areas. Two major oculomotor pathways originate from the PPRF. One pathway ascends rostrally, close to but outside of the MLF, to the rostral mesencephalon to coordinate horizontal and vertical gaze. The other pathway descends caudally and sends off a direct projection to the ipsilateral abducens nucleus. This excitatory pathway controls horizontal gaze to the ipsilateral side by stimulating motoneurons to the lateral rectus and internuclear abducens neurons, which project via the MLF to the medial rectus motoneurons of the contralateral oculomotor nucleus. Other major projections likely to be involved in gaze are projections from the PPRF to the nucleus prepositus hypoglossi and PPRF cerebellar pathways. No direct inhibitory pathway from the PPRF projects to the contralateral abducens nucleus. The inhibitory pathway from inhibitory burst neurons travels from the dorsomedial gigantocellular tegmental field just caudal to the abducens nucleus, crosses the brainstem and terminates in the contralateral abducens nucleus. The importance of this pathway has been demonstrated for saccades and quick phases of vestibular nystagmus, but it is still unclear whether an analogous pathway exists to control smooth pursuit movements. In any case, the PPRF generates all ipsilateral-directed saccades (including the quick phases of vestibular nystagmus). Abducens nucleus. The abducens nucleus contains typical motoneurons that give rise to root fibers that innervate the lateral rectus as well as internuclear neurons whose axons cross the midline and ascend via the contralateral MLF to the medial rectus subnucleus in the contralateral oculomotor (third nerve) nucleus. This projection is the main excitatory input to medial rectus motoneurons in lateral gaze. An old clinicopathologic case published by Bennett and Savill (1) described a unilateral gaze palsy with an associated "patch of softening" in the abducens nucleus without apparent involvement of neighboring structures. Clinical distinction PPRF: Abducens nucleus. At the bedside distinction can be made between the manifestations of gaze palsies in lesions of the PPRF in the upper pons from those of the PPRF in the lower pons at the level of the abducens nucleus. With PPRF lesions rostral to the abducens, there is ipsilateral paralysis of saccades and pursuit, but the eyes can be driven to the side of the gaze palsy with vestibular stimulation. At the level of the abducens nucleus, lesions of the PPRF are associated with ipsilateral gaze palsy and loss of reflex vestibular (and tonic neck) movements. This presumes that there is a critical synapse within the caudal PPRF for the vestibulo-ocular pathways or that, at the very least, the functional integrity of the PPRF at that level is necessary for vestibulo-ocular eye movements. An associated sign with abducens nuclear lesions, however is an ipsilateral "peripheral" facial palsy because the genu of the seventh nerve wraps around the abducens nucleus. The gustatory fibers are spared, because these fibers are carried in the intermediate branch of the facial nerve to the nucleus solitarius of the medulla. This sign was present in four of our MS patients (Table 2). An identical ipsilateral gaze palsy can be produced by damage to axons of abducens neurons as they course through the brainstem, namely, the ipsilateral sixth nerve fascicle and those axons which ascend the contralateral MLF. Separation of these two anatomic sites suggests two lesions. A lateral gaze palsy that always remains conjugate is consistent with one lesion of the abducens nucleus, whereas one that is not conjugate at any time would better fit two lesions. Two examples, in our patient group, were both patients with definite MS. Internuclear ophthalmoplegia Both human and experimental data have established the localization of the lesion that causes INO. A unilateral INO is due to the interruption of the ipsilateral MLF after it has crossed the midline caudally in the pons from its site of origin in the contralateral abducens nucleus. Clinically, the syndrome is characterized by: 1. Paresis or paralysis of adduction of the ipsilateral eye on attempted horizontal gaze to the contralateral side. 2. Horizontal jerk nystagmus in the contralateral abducting eye and 3. Typically convergence is intact if the lesion does not extend to the mesencephalon. Other associated findings are abnormalities in vertical smooth pursuit, OKN, the vertical VOR with normal vertical saccades if the INO is bilateral, gaze evoked vertical nystagmus on upward gaze more frequent than downgaze if the lesion is bilateral and skew deviation. The one-had-a-half syndrome is characterized by, on horizontal gaze: 1. An ipsilateral gaze paresis or palsy 2. An INO on contralateral gaze 3. At rest, an exotropia of the eye contralateral to the lesion in the acute phase, or no deviation at rest, or less commonly, an esotropia of the eye ipsilateral to the lesion resulting from paresis of the sixth nerve. Occasionally, ocular bobbing occurs, which may be periodic or limited to the ipsilateral eye. Anisocoria is also reported. Personal observation: All of our patients with the one-and-a-half syndrome showed a complete or partial ipsilateral horizontal gaze palsy and a clinical or subclinical INO on contralateral gaze. Slow and incomplete adduction of the ipsilateral eye was attributed to deficient medial rectus excitation and horizontal jerk nystagmus in the abducting eye was attributed to deficient tonic inhibition of the medial rectus. This interpretation is consistent with the results of oculographic studies. The association of exotropia in the one-and-a-half syndrome was observed by Fisher and later termed "paralytic pontine exotropia" by Sharpe et al. In this distinctive supranuclear syndrome, the deviated, exotropic eye shows abduction nystagmus during attempts to move it further laterally, and there is extreme slowness of adduction saccades when the eye is used to fixate to move it to the midline. Paralytic pontine exotropia is attributed to tonic contralateral ocular deviation of the eyes, which implies acute ipsilateral involvement of the PPRF. Failure of the ipsilateral eye to deviate medially is explained by the INO. Three autopsy cases of paralytic pontine exotropia confirm the lesion site. Esotropia of the ipsilateral eye may be due to a lesion of the fasciculus of the ipsilateral sixth nerve.The anatomic localization of the lesion in the one-and-a-half syndrome has been confirmed at autopsy in seven patients. Six of them had a single unilateral lesion in the pontine tegmentum ipsilateral to the gaze palsy involving the PPRF and the ipsilateral MLF. The abducens nucleus was spared by discrete lesions and involved in extensive lesions resulting from infarction, hemorrhage or glioma. In Fisher's case, extensive pontine infarction involved both the PPRF and the abducens nucleus. Crevits et al correlated the gaze palsy with a single discrete infarct 3 by 2 mm in diameter in the ipsilateral PPRF and MLF. The lower fascicles of the ipsilateral sixth nerve passed through the necrotic area. This was probably the smallest lesion associated with the one-and-a-half syndrome. Newman et al reported a similar clinical case, but they found an ipsilateral PPRF lesion and "ischemic necrosis in the region of the abducens nucleus, although individual neurons could be identified". Partial damage to the contralateral PPRF was also found. 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