Cavernous Angioma

Unilateral Internuclear Ophthalmoplegia; Unilateral Horizontal Gaze Palsy; Upbeat Nystagmus on Upgaze; Convergence Normal; Pendular Vertical OscillationsDiplopiaThe patient is a 19 year old sophomore who presented in 1983 with numbness of the left hand, involving initially just the fingers, and numbness and weakness of the right side of the face. He described the numbness in his hand as if it was "intensely asleep". The facial numbness involved the perioral region. Over the next five days, prior to admission (PTA), the numbness spread to involve the whole left side of his body, and extended over a greater area of the right face to involve the cheek and right side of his tongue. One day PTA, he developed a mild occipital headache and unsteadiness standing and walking. He was admitted to an outside hospital. Brain CT: The scan revealed a mass lesion in the region of the fourth ventricle which was thought to represent a brain tumor. He was transferred and admitted to the Massachusetts General Hospital. Ocular Motility on arrival: Primary position upbeat nystagmus Rotary clockwise nystagmus on gaze left Horizontal gaze evoked nystagmus on gaze right Primary position upbeat nystagmus was attributable to a lesion(s) in the region of the nucleus intercalatus and the nucleus of Roller in the perihypoglossal area of the caudal medulla. Neurological examination showed: Right lower motor neuron facial palsy (Bell's palsy) Athetoid movements of the fingers of the left hand Pronator drift of the left arm Left upper extremity ataxia on finger-nose-finger No gait ataxia Left hemisensory loss Brain CT: Right pontomedullary hemorrhage. Vertebral angiogram with angiotomography: No evidence of a vascular malformation. Suboccipital Craniectomy: On October 14, 1983 a Suboccipital Craniectomy was performed. A right pontine hemorrhage was drained. Ocular motility post-operatively: • Right internuclear ophthalmoplegia with adduction weakness OD • Abducting nystagmus OS • Right horizontal gaze palsy • Upbeating nystagmus on upgaze • Full vertical gaze • Normal convergence • Right Bell's palsy This constellation of signs added up to the Fisher's one-and-a-half syndrome. Between 1983 and 1989 the patient had three further small bleeds in the unilateral pontine lesion. In 1986, he developed a right sixth nerve palsy and was readmitted to the MGH. Brain CT: Right pontine hematoma ventral to the floor of the fourth ventricle. In 1988, he was again readmitted with progressive ataxia of the left extremities. He also noted that movement, even passively, such as riding in the car resulted in a sensation of disequilibrium. Brain MRI: T1 and T2 weighted images in the axial and sagittal plane showed an arteriovenous malformation (AVM) in the pons with slight extension into the inferior aspect of the midbrain on the right side. The mass had faint increased density in the T1 and T2 weighted images in keeping with methemoglobin due to recent hemorrhage and was surrounded by areas of decreased density due to hemosiderin. The AVM, diagnosed as a cavernous angioma, produced no mass effect and the floor of the fourth ventricle was not elevated. The aqueduct was not compressed. (Figures 1 and 2) Therapy: The patient was seen by Dr. Raymond Adams who found all the neurological deficits pointed to a high pontine tegmental lesion. Dr. Adams explained to Robert that he had seen patients who had had as many as 15 bleeds without major destruction of nervous tissue and that the bleed was a venous leak with seepage of blood and not an arterial bleed. Dr. Adams recommended focal proton beam therapy. Dr. Raymond Kjellberg treated Robert with stereotactic Bragg Peak proton beam therapy. A total dose of 1,700 rads was delivered by two portals, one on each side of the head, each portal having three laminated divisions. A 19 mm beam was used. Inspite of radiation treatment, the patient continued to have recurrent bleeds and after his eleventh bleed in 1999 he developed a bilateral horizontal gaze palsy and pendular vertical oscillations, but no palatal tremor.I had the opportunity to film Robert on two occasions. In 1983, post-operatively, he had: • Right internuclear ophthalmoplegia with adduction weakness OD • Abducting nystagmus OS • Right horizontal gaze palsy • Upbeating nystagmus on upgaze • Full vertical gaze • Normal convergence • Right Bell's palsy Five years later, in 1988, he had: • A partial right internuclear ophthalmoplegia with weakness of adduction of the right eye with nystagmus • Abducting nystagmus OS • Impaired abduction OD due to a right sixth nerve palsy • Weakness of adduction OS on gaze right with gaze evoked nystagmus (consistent with a right horizontal gaze palsy) • Upbeat nystagmus on upgaze • Full vertical gaze • Normal pursuit eye movements • No facial weakness The video also shows confirmation of a paralytic esotropia of the right eye by the demonstration of abduction weakness when the right eye fixes alone.1989 Brain MRI studies are shown at the end of the video clip.The one-and-a-half syndrome first described by Fisher in 1967 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. 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. Clinical findings with PPRF lesion: • Loss of horizontal saccades towards the side of the lesion • Contralateral gaze deviation, in acute phase • Gaze-evoked nystagmus on looking contralateral to the lesion • Impaired smooth pursuit and vestibular eye movements may be preserved or impaired • Bilateral lesions cause total horizontal gaze palsy and slowing of vertical saccades 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 findings with lesion of the abducens nuclei • Loss of all conjugate movements towards the side of the lesion - "ipsilateral, horizontal gaze palsy" • Contralateral gaze deviation, in acute phase • Vergence and vertical movements are spared • In the intact hemifield of gaze, horizontal movements may be preserved, but ipsilaterally directed saccades are slow • Horizontal gaze-evoked nystagmus on looking contralaterally • Ipsilateral facial lower motor neuron palsy often associated due to involvement of the genu of the seventh cranial nerve. Damage to motor neurons, in the abducens nucleus innervating the left lateral rectus muscle or damage to the fascicular portion of the sixth nerve accounts for the ipsilateral sixth nerve palsy and esotropia. 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. 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. Abducens nucleus and contralateral medial longitudinal fasciculus (MLF) 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. Internuclear Ophthalmoplegia 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. 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.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. In another pathologically confirmed case evaluated clinically by electro-oculography, a hypertensive hemorrhage in the rostral pontine tegmentum had spread into the right basis pontis to destroy the ipsilateral PPRF and abducens nucleus.Cavernous angiomaRadiation therapy1. Bennett H, Savill TH. 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