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Global Supranuclear Paralysis of Vertical Gaze
Spencer S. Eccles Health Sciences Library University of Utah, 2007Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Global Supranuclear Paralysis of Vertical Gaze; Absent Vertical Saccades and Pursuit Movements; Intact Convergence; Convergence Retraction Nystagmus; Ocular Dysmetria; Ocular Tilt Reaction; LateropulsionPowerPoint Presentations: Thalamic Stroke and Disordered Sleep: http://library.med.utah.edu/NOVEL/Wray/PPT/Thalamic_Stroke_and_Disordered_Sleep_guest_lecture.ppt Kenneth C. Sassower, M.D. Massachusetts General Hospital Supranuclear Vertical Gaze Palsy: http://library.med.utah.edu/NOVEL/Wray/PPT/Supranuclear_Paralysis_of_Vertical_Gaze.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical SchoolDouble vision; Gait imbalanceThis case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2007. The patient is a healthy, 36 year old Lieutenant Commander in the Coast Guard who was last seen perfectly well at 2 a.m. on the day of admission. He awoke in the morning around 9 a.m. having over slept - a rare event for him and noticed immediately that his vision was "all askew" due to vertical diplopia. On his way to work he felt tilted to the left and a little off balance tending to veer to the left. His left face was slightly drooped and the left arm and leg were clumsy. When he arrived at the office he was unable to type. The fingers of his left hand were clumsy and failed to hit the keys accurately. He complained of fatigue and attributed this to working almost non-stop for two weeks at his computer to design a software program. Symptomatic Inquiry: Negative for headache, vertigo, speech disturbance, chest pain, shortness of breath or palpitations. Family History: Negative for vascular and neurological disease. On examination: BP 110/60, heart rate 53, normal rhythm. General Neurological Examination: Mild left facial droop No pronator drift and normal motor strength throughout Intact coordination with no Dysmetria Deep tendon reflexes 1+ symmetric Plantar responses flexor Sensory system intact Ocular motility showed: A global supranuclear paralysis of vertical up and downgaze (only 15 degrees up, 5 degrees down from midposition) Vertical saccadic pursuit movements were limited over a similar range of eye movement. Convergence normal Horizontal gaze full Gaze evoked nystagmus to the right Horizontal gaze to the left, mild abduction weakness Ocular Dysmetria: Right gaze to center overshoot (hypermetric) Left gaze to center undershoot (hypometric) Vertical oculocephalic movements intact Bell's reflex intact (eyes deviated up under tightly closed lids). Additional eye signs: A left Ocular tilt reaction (OTR) is a central vestibular disorder involving the vertical vestibulo-Ocular reflex in the roll plane. The key to the diagnosis of an OTR is the combination of a 1. Lateral head tilt to the left in this case. 2. Hypertropia of the undermost eye, left eye, 3. Hypertropia of the contralateral right eye. 4. Fundus photography completes the triad and shows cyclodeviation of the eyes towards the head tilt (excyclotropia of the hypotropic eye; incyclotropia of the hypertropic eye). This patient did not complain of any perceptual tilt of the visual scene or crossed double images. Optokinetic nystagmus (OKN) with rotation of the stripes down, showed convergence retraction nystagmus as he attempted to look up to refixate the stripes. The pupils were abnormal - 5 mm OU with light/near dissociation. Investigations: Initially, there was concern for a diagnosis of endocarditis given the history of recent dental work and night sweats. Blood Studies: Complete blood count and erythrocyte sedimentation rate normal. Blood cultures x 3 negative. Hemocoagulable panel normal. Echocardiogram: A transthoracic and transesophageal echo revealed a patent foramen ovale with left to right shunting by Doppler. Chest x-ray and CT: Showed a right pulmonary embolus and lower lobe infarct. Abdominal/pelvic CT: Normal. Ultrasound and MRV of the lower extremities and pelvis revealed no deep vein thrombosis (DVT). CTA of the head showed: 1. Hyperdensity in the right anterior medial thalamus, consistent with infarction. 2. No hemodynamically significant lesion in the cervical or intracranial arterial circulation 3. Three mm. hypodense nodule in the posterior aspect of the left lobe of the thyroid gland Brain MRI perfusion imaging (7/16/07): 1. A DWI hyperintensity and corresponding ADC hypointensity in the right anterior medial thalamus extending into the right parasagittal midbrain adjacent to the red nucleus. (Figure 1) 2. A very faint FLAIR hyperintensity corresponding to the restricted diffusion image in the right thalamus. Diagnosis: Unilateral embolic infarction in the right anterior medial thalamus extending into the right mesencephalon adjacent to the red nucleus. Treatment: Warfarin sodium (Coumadin) 5 MG. p.o. q. p.m. Enoxaparin (Lovenox) 70 MG SC b.i.d. Discharge Diagnosis: 1. Discreet unilateral embolic infarct of the right paramedian thalamus and upper midbrain in the distribution of the posterior thalamo-subthalamic paramedian artery - the artery of Percheron (1). 2. A clinically silent right lower lobe pulmonary embolus. 3. Patent foramen ovale (PFO) with left to right shunting. Prognosis: The patient was advised that the prognosis for full recovery of his eye movements was excellent. On day 5, the vertical diplopia had resolved with complete resolution of the OTR and skew deviation. Two months later further recovery was noted with: 1. Full vertical gaze with slow vertical saccades most marked on up gaze 2. Looking down from a full upgaze position the eyes lateropulsed to the left or converged. 3. Beats of convergence nystagmus were provoked by a fast upward saccade and OKN with the stripes down. 4. He complained of persistent somnolence and had adopted the habit of setting 3 alarm clocks to wake him each morning. The patient returned 3 months after his acute stroke for closure of the PFO. On examination three weeks later, there was no change in his eye movements. He complained of excessive day time sleepiness. Brain MRI showed a rounded focus of T2 hyperintensity along the medial aspect of the right thalamus at the same location as a lesion with restricted diffusion on the prior brain MRI. (Figures 2A, B and C)The video clips of this case were taken with a hand held digital camera 4 days after the acute stroke. The first strip shows: Complete supranuclear paralysis of saccadic and pursuit upgaze with esodeviation of the left eye as he attempts to look up. Impaired conjugate downgaze and, on attempting to look down, the eyes converge. Convergence intact Vertical oculocephalic movements intact Bell's (upward deviation of the eyes under closed eyelids) intact A second clip taken 2 months later showed: Full up and downgaze with slow saccades on upgaze only and remarkable contraversive lateropulsion of the eyes to the left on full downgaze Vertical pursuit saccadic up and down Convergence intact Normal pupilsSee aboveThree neural structures in the midbrain reticular formation are involved in the generation of vertical eye movements: • Posterior commisure (PC) • Interstitial nucleus of Cajal (INC) and • Rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) In this case all three structures were damaged by the unilateral right paramedian thalamic midbrain infarct. Damage to the riMLF, and posterior commissure explains the global supranuclear paralysis of vertical gaze. Infarction of the right INC accounts for the left OTR. The infarct interrupted the pathways involved in vertical gaze just before they decussate producing an anatomically unilateral but functionally bilateral lesion. Involvement of the pretectal nuclei in the pupillary pathway, in the dorsum midbrain accounts for light-near dissociation of the pupils, and ischemia of the periaqueductal grey accounts for convergence retraction nystagmus. Literature review: Previous cases of bidirectional vertical gaze palsy from a unilateral right upper midbrain infarct have been reported. Alemdar M et al (2) reported a 47 year old woman who developed sudden complete loss of vertical saccades, smooth pursuit, and vestibular eye movements bilaterally. MRI revealed a unilateral midbrain infarct involving the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC) and spared the posterior commissure (PC). The lesion is presumed to have interrupted the pathways involved in vertical gaze just before they decussate, inducing an anatomically unilateral but functionally bilateral lesion. Previous reports of bidirectional vertical gaze palsy have shown lesions involving the PC or both riMLFs. Alemdar's case is the first to show that a unilateral lesion of the riMLF and the INC that spares the PC may cause complete bidirectional vertical gaze palsy. Ranalli PJ et al (12) quantified the vertical gaze defect in their patient by magnetic search coil oculography and documented the marked restriction of up and down saccades with preservation of only a 15 degree range of downward movement from midposition and a similar restriction of vertical pursuit movements. This patient had, in addition to a global vertical gaze palsy: 1. An inverted Bell's with the eyes deviating down on forced eye closure. 2. Seesaw nystagmus 3. Limited convergence 4. Limited oculocephalic movements 5. The pupil reflexes are not reported At autopsy a wedge-shaped area of infarction in the right midbrain tegmentum was found, situated dorsomedial to the rostral border of the red nucleus. Its caudal extent reached 1 mm below the level of the habenulopeduncular tract (tractus retroflexus of Meynert); it extended 10.5 mm rostrally, extending in two discreet bands in the medial thalamus, adjacent to the wall of the third ventricle. (Figure 1) The infarct destroyed the prerubral region containing the riMLF, the rostral one mm of the interstitial nucleus of Cajal (INC), the nucleus of Darkschewitsth and its invested fiber tracks, the ventral portion of the nucleus of the posterior commissure (NPCE) and parts of the dorsomedial and parafascicular thalamic nuclei. The posterior commissure, the left midbrain tegmentum, and Ocular motor nuclei were spared. The rest of the brainstem and cerebellum were also normal.Infarction destroying the prerubral region of the right midbrain and the dorsomedial and parafascicular region of the right thalamus.Unilateral Embolic Infarction in the distribution of the right posterior thalamus-subthalamic paramedian artery (Type 1) associated with a PFO.Anticoagulation followed by closure of a patent foramen ovale.1. Auerbach SH, DePiero TJ, Romanul F. Sylvian aqueduct syndrome caused by unilateral midbrain lesion. Ann Neurol 1982;11:91-94. http://www.ncbi.nlm.nih.gov/pubmed/7059132 2. Alemdar M, Kamaci MD, Budak F. Unilateral midbrain infarction causing upward and downward gaze palsy. J Neuro-Ophthalmol 2006;26:173-176. http://www.ncbi.nlm.nih.gov/pubmed/16966933 3. Brandt T, Dieterich M. Pathological eye-head coordination in roll: tonic Ocular tilt reaction in mesencephalic and medullary lesions. Brain 1987;110:694-666. http://www.ncbi.nlm.nih.gov/pubmed/3495315 4. Bhidayasiri R, Plant GT, Leigh RJ. A hypothetical scheme for the brainstem control of vertical gaze. Neurology 2000;54:1985-1993. http://www.ncbi.nlm.nih.gov/pubmed/10822441 5. Bogousslavsky J,Miklossy J, Regli F, Janzer R. Vertical gaze palsy and selective unilateral infarction of rostral interstitial nucleus of the medial longitudinal fasiculus (riMLF). J Neurol Neurosurg Psychiatry 1990;53:67-71. http://www.ncbi.nlm.nih.gov/pubmed/2303833 6. Buttner-Ennever JA, Buttner U, Cohen B. Baumgartner G. Vertical gaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus. Brain 1982;105:125-149. http://www.ncbi.nlm.nih.gov/pubmed/7066670 7. Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw JJ, Lyon-Caen O. Paramedian thalamic and midbrain infarcts; clinical and neuropathological study. Ann Neurol 1981;10:127-148. http://www.ncbi.nlm.nih.gov/pubmed/7283400 8. Halmagyi GM, Brandt T, Dieterich M, Curthoys IS, Stark RJ, Hoyt WF. Tonic contraversive Ocular tilt reaction due to unilateral meso-diencephalic lesion. Neurology 1990;40:1503-1509. http://www.ncbi.nlm.nih.gov/pubmed/2215939 9. Hommel M., Bogousslavsky J. The spectrum of vertical gaze palsy following unilateral brainstem stroke. Neurology 1991;41:1229-1234. http://www.ncbi.nlm.nih.gov/pubmed/1866011 10. Percheron G. Les artères du thalamus humain. II Artères et territores thalamiques paramédians de l'artère basilaire communicante. Rev Neurol 1976;132:309-324. 11. Pierrot-Deselligny C. Chain F, Gray F, Serdaru M, Escourolle R, Lhermitte F. Parinaud's syndrome: electrooculographic and anatomical analyses of six vascular cases with deductions about vertical gaze organization in the premotor structures. Brain 1982;105:667-696. http://www.ncbi.nlm.nih.gov/pubmed/7139250 12. Ranalli PJ, Sharpe JA, Fletcher WA. Palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations. Neurol 1988; 38(1):114-122. http://www.ncbi.nlm.nih.gov/pubmed/3336442 13. Seifert T, Enzinger C, Ropele S, Storch MK, Fazekas F. Midbrain ischemia presenting as vertical gaze palsy; value of diffusion-weighted magnetic resonance imaging. Cerebrovasc Dis 2004;18:3-7. http://www.ncbi.nlm.nih.gov/pubmed/15159614 14. Trojanowski JQ, Wray SH. Vertical gaze ophthalmoplegia: selective paralysis of downgaze. Neurology 1980;30:605-610. http://www.ncbi.nlm.nih.gov/pubmed/7189837MTemspverticalgazepals
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Bilateral Sixth Nerve Palsy
Spencer S. Eccles Health Sciences Library University of Utah, 1997Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Bilateral Sixth Nerve Palsy; Bilateral Esotropia; Paraneoplastic Opsoclonus/FlutterDouble Vision and ataxiaThis patient is a 62 year old woman with a six month history of double vision and difficulty walking. In August 1996, she first noted her right upper eyelid twitching followed by dizziness, nausea and vomiting. Soon after her voice became "shaky" and she experienced mild difficulty walking. She consulted her primary care physician and was prescribed Zoloft for depression. In November 1996, she developed double vision, and increasing unsteadiness walking. In December 1996, she consulted a neurologist. Brain MRI at an outside hospital reported to be normal In January 1997, she was admitted to Massachusetts General Hospital. Past History: Significant for right breast cancer in 1986, status post lumpectomy and radiation therapy. Family History: Negative for neurologic disease Neurological examination: Normal cognitive function Mild dysarthria and tremulous voice Spontaneous myoclonus and bilateral hand tremors Mild left hemiparesis with hyperreflexia and extensor plantar response Right flexor plantar response Bilateral limb ataxia and gait ataxia Neuro-ophthalmological examination: Visual acuity 20/20 OU Visual fields, pupils and fundus examination no abnormality Ocular Motility: • Intermittent opsoclonus with multivectorial conjugate saccades without an intersaccadic interval and • Ocular flutter with horizontal back to back saccades in central gaze • Esotropia OS > OD • Weakness of abduction OS - left sixth nerve palsy • Weakness of adduction OS • Weakness of abduction OD - right sixth nerve palsy • Full upgaze with upbeat nystagmus • Full downgaze with no nystagmus • Pursuit movements normal. Testing for Ocular Dysmetria show slow refixation saccades. No Dysmetria. Diagnosis: Paraneoplastic cerebellar syndrome with opsoclonus/flutter. 1/27/97 Brain MRI: The following sequences were obtained: Axial FLAIR, T1, FSE T2, Diffusion weighted images and post gadolinium. The study showed areas of T2 and FLAIR hyperintensity involving the tegmen and extending cranially to the midbrain adjacent to the midline and just inferior to the cerebellar peduncle. Also noted were areas of FLAIR and T2 hyperintensity within the corona radiata and centrum semiovale bilaterally, left greater than right. Similar signal abnormalities were seen within the right putamen and globus pallidus. Impression: Diffuse demyelinating process consistent with a paraneoplastic syndrome. Lumbar Puncture: Cerebrospinal fluid protein 36 mg/dl Sugar 68 mg/dl 136 RBC 12 WBC 95% lymphs 4% monocytes Positive for oligoclonal bands Cytology was negative for malignant cells twice Chest/abdomen/pelvic CT Normal Bone scan and bone marrow biopsy: Normal Mammogram: Bilateral mammogram Cluster of microcalcifications in the subareolar region of the lateral aspect of the left breast suspicious for intraductal carcinoma. Procedure: A needle guided left breast biopsy Pathology: Intraductal adenocarcinoma in situ in the left breast. The primary breast cancer being in the right breast. Paraneoplastic Markers: CSF and serum were sent to Dr. Posner at the Memorial Sloane Kettering Cancer Center for antibody studies (Anti-Ri, Anti-Yo). No antibodies were detected. Ri Autoantibody Test - Negative Anti-Ri is a highly specific antineuronal antibody that reacts with nuclei of neurons in the central nervous system. The presence of anti-Ri antibody identifies the subset of patients with paraneoplastic ataxia and opsoclonus who suffer from breast or other gynecological cancer. The antibody when present is a useful marker for this type of underlying malignancy. The relative amount of anti-Ri was found to be always higher in CSF than in serum. 1. Anderson NE et al. Ann Neurol 1988;24:559-567 2. Budde-Steffen C. et al. Ann Neurol 1988;23:528-531. 3. Luque A. et al. Ann Neurol 1989;26:178 (Abstract) All diagnostic antibody tests should be considered within the context of clinical findings. 1. Dalmau et al. 1992 Medicine 71:2;59-72. Diagnosis: 1. Paraneoplastic opsoclonus/Ocular flutter 2. Paraneoplastic cerebellar syndrome 3. Paraneoplastic brainstem encephalitis 4. Bilateral sixth nerve palsy 5. Intraductal adenocarcinoma in situ left breast Surgical resection of the intraductal adenocarcinoma in situ was done. Therapy: Ten days of IV solumedrol 1 gm per day Five day course of IV IgG For an overview of paraneoplastic opsoclonus/flutter review: ID931-1 Paraneoplastic opsoclonus/CA breast, ID936-7 Paraneoplastic Ocular flutter/CA lung. Hospital Course: Over a period of ten days the opsoclonus and flutter completely resolved and there was significant improvement in her ophthalmoplegia. The left eye regained almost full abduction and the right eye was able to cross the midline looking right. The spontaneous myoclonus stopped, hand tremors waxed and waned but overall improved, and the gait instability was markedly improved. She was able to walk in her room without a walker and in the hallway with a wheeled walker. She was hospitalized for three weeks and then discharged to a rehabilitation hospital. Discharge medication: Prednisone 10 mg daily, three times a day and on a tapering dose to stop after two weeks. The patient was followed by the neuro-oncology team.This 62 year old woman with paraneoplastic opsoclonus/flutter and diplopia due to bilateral sixth nerve palsy describes the visual disturbance of oscillopsia. At the time the video was made she had no opsoclonus/flutter. The eyes show: • Esotropia OS > OD • Weakness of abduction OS - left sixth nerve palsy • Weakness of abduction OD - right sixth nerve palsy • Impaired adduction OS • Full upgaze with upbeat nystagmus • Full downgaze with no nystagmus • Pursuit movements normal. Testing for Ocular Dysmetria show slow refixation saccades. No Dysmetria. In addition this patient had • Bilateral ataxia on finger/nose test and heel-knee-shin • Loss of rhythm hand tapping • Gait ataxia Ocular flutter and flutter Dysmetria are the major diagnostic signs. • Intermittent epochs of Ocular flutter - horizontal back-to-back saccadic oscillations without an intersaccadic interval. • Flutter Dysmetria most evident when the eyes make voluntary saccadic movements to the left Occasionally the amplitude of flutter is very small - microflutter, and the oscillations only detected with an ophthalmoscope or eye movement recordings. (6). Ocular flutter is often associated with paraneoplastic opsoclonus. Comment Dr. Zee (DZ), March 2007 SHW: David, I neglected to test for Ocular flutter under closed lids by asking the patient to look to the right and back to center and to the left and back to center. Would I expect to see flutter with eyes closed? DZ: Good question. This would seem to be very likely since eye closure shuts off the pause cells, and flutter itself can often be triggered by making a saccade, even in the light.Neuroimaging studies are unavailable in this case. Illustrative brain MRI scans in another patient with paraneoplastic opsoclonus/Ocular flutter are shown here. Axial FLAIR shows hyperintensity in both cerebellar hemispheres. Axial FLAIR through the mid-pons shows striking signal abnormality in the dorsal pons and cerebellar hemispheres. Axial FLAIR scan through the upper pons shows paraneoplastic brainstem multifocal hyperintensities consistent with encephalitis. (Courtesy of Anne Osborn, M.D.)Paraneoplastic opsoclonus/Ocular flutter is thought to be humorally mediated, and antibodies to diverse auto-antigens have been reported, but most patients are seronegative as in this case. The antineural antibodies associated with opsoclonus include Anti-Ri, Anti-Hu, Anti-Yo, Anti-Mal, and Anti-amphyphisin antibodies. With regard to opsoclonus (OC), it is not known whether OC is a cerebellar or brainstem disorder. (Review case ID931-1 the index case for the Anti-Ri antibody and ID936-7 Paraneoplastic Ocular flutter). Cerebellum: Wong et al have suggested, on theoretical grounds, that the deep cerebellar nuclei should be activated in patients with opsoclonus. (9) Helmchen et al (7) assessed this hypothesis with fMRI in two patients with opsoclonus and compared them with healthy subjects. They used three-dimensional (3D) scleral search coil recordings to characterize the pathologic eye oscillations. Fortuitously, both patients showed a decrease of or no OC with the eyes closed, so fMRI signals under two conditions (open eyes with OC vs closed eyes without OC) could be compared. A comparison of these two states revealed neither cerebellar vermal nor brainstem activation but showed, for the first time, bilateral functional activation of the deep cerebellar fastigial nuclei. This result supports Wong et al's recent hypothesis that OC results from a disinhibition of the fastigial Ocular motor region (FOR). FOR contains saccade-related neurons that augment the ongoing discharge of pontine excitory and inhibitory burst neurons. Because the cerebellar Ocular motor vermis physiologically inhibits FOR, the authors concluded that the absence of vermal activation during OC may reflect a cause of OC. Brainstem: Glycine has been identified as the neurotransmitter of omnipause neurons and poisoning with a glycine antagonist, strychnine, is reported to produce opsoclonus and myoclonus. Zee postulates that an immune-mediated Glycine Channelopathy affecting the membrane of omnipause cells may be the underlying mechanism for Ocular flutter and opsoclonus and that it may be possible that membrane-stabilizing drugs may have a therapeutic role for flutter and opsoclonus in the future. (Personal communication, 2007) (For further discussion see ref 8).Intraductal adenocarcinoma of the breastImmune modulation - intravenous IgG1. Alderson LM. Neurologic complications of breast cancer. In: Office Practice of Neurology 2nd Edition. Eds. Samuels MA, Feske SK. Churchill Livingston, 2003; 184:1181-1186. 2. Anderson NE. Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration: clinical-immunological correlations. Ann Neurol 1988;24:559-567. http://www.ncbi.nlm.nih.gov/pubmed/3239956 3. Bataller L, Dalmau J. Paraneoplastic Neurologic Syndromes: Approaches to Diagnosis and Treatment. Semin Neurol 2003;23:215-224. http://www.ncbi.nlm.nih.gov/pubmed/12894387 4. Budde-Steffen C, Anderson NE, Rosenblum MK, Graus F., Ford, D, Synek, BJL, Wray, SH, Posner JB. An anti-neuronal autoantibody in paraneoplastic opsoclonus. Ann Neurol 1988;23:528-531. http://www.ncbi.nlm.nih.gov/pubmed/3389761 5. Cogan DG. Ocular Dysmetria, flutter-like oscillations of the eyes and opsoclonus. Arch. Ophthalmol 1954;51:318. http://www.ncbi.nlm.nih.gov/pubmed/13123617 7. Helmchen C, Rambold H, Sprenger A, Erdmann C, Binkofski F. Cerebellar activation in opsoclonus: An fMRI study. Neurology 2003;61:412-415. http://www.ncbi.nlm.nih.gov/pubmed/12913213 8. Leigh RJ, Zee DS. Diagnosis of Pheripheral Ocular Motor Palsies and Strabismus Chp 9:385-474. In The Neurology of Eye Movements. 4th Ed. Oxford University Press, New York 2006. 9. Wong AM, Musallam S, Tomlinson RD, Shannon P, Sharpe JA. Opsoclonus in three dimensions: oculographic, neuropathologic and modeling correlates. J Neurol Sci 2001;189:71-81. http://www.ncbi.nlm.nih.gov/pubmed/1153523
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Benign Neonatal Ocular Flutter
Spencer S. Eccles Health Sciences Library University of Utah, 1994Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Ocular FlutterJiggling EyesShortly after birth, this baby was noted to have "jiggling eyes" by his mother. He was in good general health and neurologically intact. Cogan and I saw the baby and Cogan made the diagnosis of neonatal Ocular flutter. In 1954 Cogan first used the term "Ocular flutter" to describe a rare disorder of horizontal eye movements characterized by rapid bursts of synchronous back-to-back horizontal oscillatory movements usually seen in the primary position of gaze. Since then, there have been over 50 reports, usually single cases or small series, linking the phenomenon to a wide variety of brainstem and cerebellar conditions, e.g. post enteroviral infection, cerebral malaria, cyclosporine treatment and meningitis, but perhaps most frequently associated with parainfectious states or, with opsoclonus, as a paraneoplastic manifestation of occult malignancy. Benign neonatal Ocular flutter should only be diagnosed when all other potential etiologies have been ruled out by appropriate investigations.This baby has benign neonatal Ocular flutter. Watch this baby's eyes carefully for very short bursts of very fast conjugate horizontal back-to-back saccades without an intersaccadic interval. This tape is an excellent example of a case of benign neonatal Ocular flutter. At this time, bursts of flutter were less frequent and shorter in duration than on his initial visit, three weeks previous to this recording. Ocular flutter resolved completely over the next six weeks. Idiopathic opsoclonus can however occur as a transient phenomenon in an otherwise normal infant.1. Ashe J, Hain TC, Zee DS, Schatz NJ. Microsaccadic flutter. Brain 1991;114:461-472. http://www.ncbi.nlm.nih.gov/pubmed/2004251 2. Cogan DG. Ocular Dysmetria: flutter like oscillations of the eyes and opsoclonus. Arch Ophthalmol 1954;51:318-335. http://www.ncbi.nlm.nih.gov/pubmed/13123617 3. Dyken P, Kolar O. Dancing eye dancing feet: Infantile polymyoclonia. Brain 1968; 91:305-320. http://www.ncbi.nlm.nih.gov/pubmed/5721932 4. Hankey GJ, Sadka M. Ocular flutter postural body tremulousness and CSF pleocytosis: a rare postinfectious syndrome. J Neurol Neurosurg Psychiatry 1987;50:1235-1236. http://www.ncbi.nlm.nih.gov/pubmed/3668576 5. Hoyt CS, Mousel DK, Weber AA. Transient supranuclear disorders of gaze in healthy neonates. Am J Ophthalmol 1980;89:708-711. http://www.ncbi.nlm.nih.gov/pubmed/7377270 6. Hoyt CS, Gelbart SS. Vertical mystagmus in infants with congenital Ocular abnormalities. Ophthalmic Pediatr Genet 1984;4:155-162. http://www.ncbi.nlm.nih.gov/pubmed/6443616 7. Kinsbourne M. Myoclonic encephalopathy of infants. J Neurol Neurosurg Psychiatry 1962;25:2712-276. http://www.ncbi.nlm.nih.gov/pubmed/21610907 8. Kuban KC, Ephros MA, Freeman RL, Laffell LB, Bresnan MJ. Syndrome of opsoclonus-myoclonus caused by Coxsackie B3 infection. Ann Neurol 1983;13:69-71. http://www.ncbi.nlm.nih.gov/pubmed/6299176 9. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusion. Chp 10:475-558. In: The Neurology of Eye Movements, Fourth Edition. Oxford University Press, NY. 2006. 10. Orzechowski K, Walichiewicz T. Przypadek operowanej torbieli srodpajeczy mozdika (operated cyst of the cerebellum) Licowski Tygodnik Lekurski 1913;18:219-227. 11. Pranzatelli MR, Tate ED, Travelstead AL, Longee D. Immunologic and clinical responses to rituximab in a child with opsoclonus-myoclonus syndrome. Pediatrics 2005;115:115-119. http://www.ncbi.nlm.nih.gov/pubmed/15601813 12. Shawkat FS, Harris CM, Wilson J, Taylor DSI. Eye movements in children with opsoclonus. Neuropaediatrics 1993;24:218-223. http://www.ncbi.nlm.nih.gov/pubmed/8232781 13. Wiest G, Safoschnik G, Schnaberth G, Mueller C. Ocular flutter and truncal ataxia may be associated with enterovirus infection. J Neurology 1997, 244:288-292. http://www.ncbi.nlm.nih.gov/pubmed/917815
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Upbeat_Nystagmus
Spencer S. Eccles Health Sciences Library University of Utah, 1Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:The patient, a 36 year old Italian, presented in October 1967, at the age of 27, with acute dizziness and ataxia. He was evaluated in Rome. A pneumoencephalogram showed hydrocephalus, attributed to arachnoiditis, and a ventriculo-atrial shunt was placed. Three months post shunt placement he had a return of dizziness and ataxia accompanied by daily bi-occipital headache, diplopia, clumsiness and weakness of the left arm. In January 1968, he was readmitted and a large tumor of the left cerebellar hemisphere with invasion of the vermis was biopsied. A diagnosis of glioblastoma multiforme was made. He was treated with radiation therapy. Post operatively his major deficits were Ocular Dysmetria, left limb and gait ataxia. In 1970 he immigrated to the US. In 1971 he was referred to Dr. William Sweet, Chief of Neurosurgery at the Massachusetts General Hospital (MGH) with increasing gait ataxia and oscillopsia. Neurological examination: Cranial nerves intact (apart from the eye movements) Motor strength normal Decreased tone in the left extremities Reflexes 2+ throughout with flexor/plantar responses. Coordination: ataxia left extremities Gait ataxia, Romberg negative. Sensory examination normal. Neuro-ophthalmological examination: Visual acuity 20/20 OU Visual fields and pupils normal Fundus exam showed bilateral optic disc drusen Eye movements: •Upbeat nystagmus in primary gaze, increased on up gaze •Square wave jerks •Horizontal gaze evoked nystagmus left > right •Full vertical gaze •Upbeat nystagmus on upgaze •No nystagmus on downgaze •Pursuit, (horizontal and vertical) smooth to a very slow target, markedly saccadic to a fast target •Convergence normal •Marked saccadic hypermetria Right gaze to center overshoot (hypermetria) taking the eyes almost fully to the left Left gaze to center hypermetria taking the eyes almost fully to the right Upgaze to center hypermetria Downgaze to center hypermetria CT scan: In the region of the vermis and the medial portion of the left hemisphere there was an area of high absorption with contrast enhancement involving the cerebellar vermis and medial left cerebellar hemisphere with an apparent associated cystic component consistent with recurrent tumor. Cerebral Arteriogram: A cerebral arteriogram confirmed a highly vascular tumor of the inferior portion of the midline of the cerebellum, bulging into the fourth ventricle. Pathology: The slides from the original biopsy were obtained from Rome and reviewed by Dr E. P. Richardson, Chief of Neuropathology at the MGH. Diagnosis: A high-grade astrocytoma grade 3-4. Surgical procedure: A posterior fossa craniotomy was performed. To access the tumor, the most inferior aspect of the vermis was split to reach the roof of the 4th ventricle. In so doing, a well demarcated tumor nodule was found extending to both sides of the cerebellum, mostly to the left side. It was possible to separate the superior most aspect of the tumor easily from the 4th ventricle. Several small branches of the posterior inferior cerebellar arteries had to be divided to devascularize the tumor which was then gently dissected away from the floor of the 4th ventricle. At the end, the surgeon felt he had as close to a grossly total removal of the tumor as was possible and no visible tumor was left behind. Post operative status: The patient made a good post-operative recovery and was able to walk with an elbow crutch. He continued to be followed by neurosurgery until he was 66 years of age. During that time he had required a shunt revision on two occasions and therapy for an episode of meningitis/cerebritis. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/28
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Supranuclear_Paralysis_of_Vertical_Gaze
Spencer S. Eccles Health Sciences Library University of Utah, 1Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:This case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2007. The patient is a healthy, 36 year old Lieutenant Commander in the Coast Guard who was last seen perfectly well at 2 a.m. on the day of admission. He awoke in the morning around 9 a.m. having over slept - a rare event for him and noticed immediately that his vision was "all askew" due to vertical diplopia. On his way to work he felt tilted to the left and a little off balance tending to veer to the left. His left face was slightly drooped and the left arm and leg were clumsy. When he arrived at the office he was unable to type. The fingers of his left hand were clumsy and failed to hit the keys accurately. He complained of fatigue and attributed this to working almost non-stop for two weeks at his computer to design a software program. Symptomatic Inquiry: Negative for headache, vertigo, speech disturbance, chest pain, shortness of breath or palpitations. Family History: Negative for vascular and neurological disease. On examination: BP 110/60, heart rate 53, normal rhythm. General Neurological Examination: Mild left facial droop No pronator drift and normal motor strength throughout Intact coordination with no Dysmetria Deep tendon reflexes 1+ symmetric Plantar responses flexor Sensory system intact Ocular motility showed: A global supranuclear paralysis of vertical up and downgaze (only 15 degrees up, 5 degrees down from midposition) Vertical saccadic pursuit movements were limited over a similar range of eye movement. Convergence normal Horizontal gaze full Gaze evoked nystagmus to the right Horizontal gaze to the left, mild abduction weakness Ocular Dysmetria: Right gaze to center overshoot (hypermetric) Left gaze to center undershoot (hypometric) Vertical oculocephalic movements intact Bell's reflex intact (eyes deviated up under tightly closed lids). Additional eye signs: A left Ocular tilt reaction (OTR) is a central vestibular disorder involving the vertical vestibulo-Ocular reflex in the roll plane. The key to the diagnosis of an OTR is the combination of a 1.Lateral head tilt to the left in this case. 2.Hypertropia of the undermost eye, left eye, 3.Hypertropia of the contralateral right eye. 4.Fundus photography completes the triad and shows cyclodeviation of the eyes towards the head tilt (excyclotropia of the hypotropic eye; incyclotropia of the hypertropic eye). This patient did not complain of any perceptual tilt of the visual scene or crossed double images. Optokinetic nystagmus (OKN) with rotation of the stripes down, showed convergence retraction nystagmus as he attempted to look up to refixate the stripes. The pupils were abnormal - 5 mm OU with light/near dissociation. Investigations: Initially, there was concern for a diagnosis of endocarditis given the history of recent dental work and night sweats. Blood Studies: Complete blood count and erythrocyte sedimentation rate normal. Blood cultures x 3 negative. Hemocoagulable panel normal. Echocardiogram: A transthoracic and transesophageal echo revealed a patent foramen ovale with left to right shunting by Doppler. Chest x-ray and CT: Showed a right pulmonary embolus and lower lobe infarct. Abdominal/pelvic CT: Normal. Ultrasound and MRV of the lower extremities and pelvis revealed no deep vein thrombosis (DVT). CTA of the head showed: 1.Hyperdensity in the right anterior medial thalamus, consistent with infarction. 2.No hemodynamically significant lesion in the cervical or intracranial arterial circulation 3.Three mm. hypodense nodule in the posterior aspect of the left lobe of the thyroid gland Brain MRI perfusion imaging (7/16/07): 1.A DWI hyperintensity and corresponding ADC hypointensity in the right anterior medial thalamus extending into the right parasagittal midbrain adjacent to the red nucleus. (Figure 1) 2.A very faint FLAIR hyperintensity corresponding to the restricted diffusion image in the right thalamus. Diagnosis: Unilateral embolic infarction in the right anterior medial thalamus extending into the right mesencephalon adjacent to the red nucleus. Treatment: Warfarin sodium (Coumadin) 5 MG. p.o. q. p.m. Enoxaparin (Lovenox) 70 MG SC b.i.d. Discharge Diagnosis: 1.Discreet unilateral embolic infarct of the right paramedian thalamus and upper midbrain in the distribution of the posterior thalamo-subthalamic paramedian artery - the artery of Percheron (1). 2.A clinically silent right lower lobe pulmonary embolus. 3.Patent foramen ovale (PFO) with left to right shunting. Prognosis: The patient was advised that the prognosis for full recovery of his eye movements was excellent. On day 5, the vertical diplopia had resolved with complete resolution of the OTR and skew deviation. Two months later further recovery was noted with: 1.Full vertical gaze with slow vertical saccades most marked on up gaze 2.Looking down from a full upgaze position the eyes lateropulsed to the left or converged. 3.Beats of convergence nystagmus were provoked by a fast upward saccade and OKN with the stripes down. 4.He complained of persistent somnolence and had adopted the habit of setting 3 alarm clocks to wake him each morning. The patient returned 3 months after his acute stroke for closure of the PFO. On examination three weeks later, there was no change in his eye movements. He complained of excessive day time sleepiness. Brain MRI showed a rounded focus of T2 hyperintensity along the medial aspect of the right thalamus at the same location as a lesion with restricted diffusion on the prior brain MRI. (Figures 2A, B and C). See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/29
Shirley H. Wray - One of the best experts on this subject based on the ideXlab platform.
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Global Supranuclear Paralysis of Vertical Gaze
Spencer S. Eccles Health Sciences Library University of Utah, 2007Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Global Supranuclear Paralysis of Vertical Gaze; Absent Vertical Saccades and Pursuit Movements; Intact Convergence; Convergence Retraction Nystagmus; Ocular Dysmetria; Ocular Tilt Reaction; LateropulsionPowerPoint Presentations: Thalamic Stroke and Disordered Sleep: http://library.med.utah.edu/NOVEL/Wray/PPT/Thalamic_Stroke_and_Disordered_Sleep_guest_lecture.ppt Kenneth C. Sassower, M.D. Massachusetts General Hospital Supranuclear Vertical Gaze Palsy: http://library.med.utah.edu/NOVEL/Wray/PPT/Supranuclear_Paralysis_of_Vertical_Gaze.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical SchoolDouble vision; Gait imbalanceThis case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2007. The patient is a healthy, 36 year old Lieutenant Commander in the Coast Guard who was last seen perfectly well at 2 a.m. on the day of admission. He awoke in the morning around 9 a.m. having over slept - a rare event for him and noticed immediately that his vision was "all askew" due to vertical diplopia. On his way to work he felt tilted to the left and a little off balance tending to veer to the left. His left face was slightly drooped and the left arm and leg were clumsy. When he arrived at the office he was unable to type. The fingers of his left hand were clumsy and failed to hit the keys accurately. He complained of fatigue and attributed this to working almost non-stop for two weeks at his computer to design a software program. Symptomatic Inquiry: Negative for headache, vertigo, speech disturbance, chest pain, shortness of breath or palpitations. Family History: Negative for vascular and neurological disease. On examination: BP 110/60, heart rate 53, normal rhythm. General Neurological Examination: Mild left facial droop No pronator drift and normal motor strength throughout Intact coordination with no Dysmetria Deep tendon reflexes 1+ symmetric Plantar responses flexor Sensory system intact Ocular motility showed: A global supranuclear paralysis of vertical up and downgaze (only 15 degrees up, 5 degrees down from midposition) Vertical saccadic pursuit movements were limited over a similar range of eye movement. Convergence normal Horizontal gaze full Gaze evoked nystagmus to the right Horizontal gaze to the left, mild abduction weakness Ocular Dysmetria: Right gaze to center overshoot (hypermetric) Left gaze to center undershoot (hypometric) Vertical oculocephalic movements intact Bell's reflex intact (eyes deviated up under tightly closed lids). Additional eye signs: A left Ocular tilt reaction (OTR) is a central vestibular disorder involving the vertical vestibulo-Ocular reflex in the roll plane. The key to the diagnosis of an OTR is the combination of a 1. Lateral head tilt to the left in this case. 2. Hypertropia of the undermost eye, left eye, 3. Hypertropia of the contralateral right eye. 4. Fundus photography completes the triad and shows cyclodeviation of the eyes towards the head tilt (excyclotropia of the hypotropic eye; incyclotropia of the hypertropic eye). This patient did not complain of any perceptual tilt of the visual scene or crossed double images. Optokinetic nystagmus (OKN) with rotation of the stripes down, showed convergence retraction nystagmus as he attempted to look up to refixate the stripes. The pupils were abnormal - 5 mm OU with light/near dissociation. Investigations: Initially, there was concern for a diagnosis of endocarditis given the history of recent dental work and night sweats. Blood Studies: Complete blood count and erythrocyte sedimentation rate normal. Blood cultures x 3 negative. Hemocoagulable panel normal. Echocardiogram: A transthoracic and transesophageal echo revealed a patent foramen ovale with left to right shunting by Doppler. Chest x-ray and CT: Showed a right pulmonary embolus and lower lobe infarct. Abdominal/pelvic CT: Normal. Ultrasound and MRV of the lower extremities and pelvis revealed no deep vein thrombosis (DVT). CTA of the head showed: 1. Hyperdensity in the right anterior medial thalamus, consistent with infarction. 2. No hemodynamically significant lesion in the cervical or intracranial arterial circulation 3. Three mm. hypodense nodule in the posterior aspect of the left lobe of the thyroid gland Brain MRI perfusion imaging (7/16/07): 1. A DWI hyperintensity and corresponding ADC hypointensity in the right anterior medial thalamus extending into the right parasagittal midbrain adjacent to the red nucleus. (Figure 1) 2. A very faint FLAIR hyperintensity corresponding to the restricted diffusion image in the right thalamus. Diagnosis: Unilateral embolic infarction in the right anterior medial thalamus extending into the right mesencephalon adjacent to the red nucleus. Treatment: Warfarin sodium (Coumadin) 5 MG. p.o. q. p.m. Enoxaparin (Lovenox) 70 MG SC b.i.d. Discharge Diagnosis: 1. Discreet unilateral embolic infarct of the right paramedian thalamus and upper midbrain in the distribution of the posterior thalamo-subthalamic paramedian artery - the artery of Percheron (1). 2. A clinically silent right lower lobe pulmonary embolus. 3. Patent foramen ovale (PFO) with left to right shunting. Prognosis: The patient was advised that the prognosis for full recovery of his eye movements was excellent. On day 5, the vertical diplopia had resolved with complete resolution of the OTR and skew deviation. Two months later further recovery was noted with: 1. Full vertical gaze with slow vertical saccades most marked on up gaze 2. Looking down from a full upgaze position the eyes lateropulsed to the left or converged. 3. Beats of convergence nystagmus were provoked by a fast upward saccade and OKN with the stripes down. 4. He complained of persistent somnolence and had adopted the habit of setting 3 alarm clocks to wake him each morning. The patient returned 3 months after his acute stroke for closure of the PFO. On examination three weeks later, there was no change in his eye movements. He complained of excessive day time sleepiness. Brain MRI showed a rounded focus of T2 hyperintensity along the medial aspect of the right thalamus at the same location as a lesion with restricted diffusion on the prior brain MRI. (Figures 2A, B and C)The video clips of this case were taken with a hand held digital camera 4 days after the acute stroke. The first strip shows: Complete supranuclear paralysis of saccadic and pursuit upgaze with esodeviation of the left eye as he attempts to look up. Impaired conjugate downgaze and, on attempting to look down, the eyes converge. Convergence intact Vertical oculocephalic movements intact Bell's (upward deviation of the eyes under closed eyelids) intact A second clip taken 2 months later showed: Full up and downgaze with slow saccades on upgaze only and remarkable contraversive lateropulsion of the eyes to the left on full downgaze Vertical pursuit saccadic up and down Convergence intact Normal pupilsSee aboveThree neural structures in the midbrain reticular formation are involved in the generation of vertical eye movements: • Posterior commisure (PC) • Interstitial nucleus of Cajal (INC) and • Rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) In this case all three structures were damaged by the unilateral right paramedian thalamic midbrain infarct. Damage to the riMLF, and posterior commissure explains the global supranuclear paralysis of vertical gaze. Infarction of the right INC accounts for the left OTR. The infarct interrupted the pathways involved in vertical gaze just before they decussate producing an anatomically unilateral but functionally bilateral lesion. Involvement of the pretectal nuclei in the pupillary pathway, in the dorsum midbrain accounts for light-near dissociation of the pupils, and ischemia of the periaqueductal grey accounts for convergence retraction nystagmus. Literature review: Previous cases of bidirectional vertical gaze palsy from a unilateral right upper midbrain infarct have been reported. Alemdar M et al (2) reported a 47 year old woman who developed sudden complete loss of vertical saccades, smooth pursuit, and vestibular eye movements bilaterally. MRI revealed a unilateral midbrain infarct involving the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC) and spared the posterior commissure (PC). The lesion is presumed to have interrupted the pathways involved in vertical gaze just before they decussate, inducing an anatomically unilateral but functionally bilateral lesion. Previous reports of bidirectional vertical gaze palsy have shown lesions involving the PC or both riMLFs. Alemdar's case is the first to show that a unilateral lesion of the riMLF and the INC that spares the PC may cause complete bidirectional vertical gaze palsy. Ranalli PJ et al (12) quantified the vertical gaze defect in their patient by magnetic search coil oculography and documented the marked restriction of up and down saccades with preservation of only a 15 degree range of downward movement from midposition and a similar restriction of vertical pursuit movements. This patient had, in addition to a global vertical gaze palsy: 1. An inverted Bell's with the eyes deviating down on forced eye closure. 2. Seesaw nystagmus 3. Limited convergence 4. Limited oculocephalic movements 5. The pupil reflexes are not reported At autopsy a wedge-shaped area of infarction in the right midbrain tegmentum was found, situated dorsomedial to the rostral border of the red nucleus. Its caudal extent reached 1 mm below the level of the habenulopeduncular tract (tractus retroflexus of Meynert); it extended 10.5 mm rostrally, extending in two discreet bands in the medial thalamus, adjacent to the wall of the third ventricle. (Figure 1) The infarct destroyed the prerubral region containing the riMLF, the rostral one mm of the interstitial nucleus of Cajal (INC), the nucleus of Darkschewitsth and its invested fiber tracks, the ventral portion of the nucleus of the posterior commissure (NPCE) and parts of the dorsomedial and parafascicular thalamic nuclei. The posterior commissure, the left midbrain tegmentum, and Ocular motor nuclei were spared. The rest of the brainstem and cerebellum were also normal.Infarction destroying the prerubral region of the right midbrain and the dorsomedial and parafascicular region of the right thalamus.Unilateral Embolic Infarction in the distribution of the right posterior thalamus-subthalamic paramedian artery (Type 1) associated with a PFO.Anticoagulation followed by closure of a patent foramen ovale.1. Auerbach SH, DePiero TJ, Romanul F. Sylvian aqueduct syndrome caused by unilateral midbrain lesion. Ann Neurol 1982;11:91-94. http://www.ncbi.nlm.nih.gov/pubmed/7059132 2. Alemdar M, Kamaci MD, Budak F. Unilateral midbrain infarction causing upward and downward gaze palsy. J Neuro-Ophthalmol 2006;26:173-176. http://www.ncbi.nlm.nih.gov/pubmed/16966933 3. Brandt T, Dieterich M. Pathological eye-head coordination in roll: tonic Ocular tilt reaction in mesencephalic and medullary lesions. Brain 1987;110:694-666. http://www.ncbi.nlm.nih.gov/pubmed/3495315 4. Bhidayasiri R, Plant GT, Leigh RJ. A hypothetical scheme for the brainstem control of vertical gaze. Neurology 2000;54:1985-1993. http://www.ncbi.nlm.nih.gov/pubmed/10822441 5. Bogousslavsky J,Miklossy J, Regli F, Janzer R. Vertical gaze palsy and selective unilateral infarction of rostral interstitial nucleus of the medial longitudinal fasiculus (riMLF). J Neurol Neurosurg Psychiatry 1990;53:67-71. http://www.ncbi.nlm.nih.gov/pubmed/2303833 6. Buttner-Ennever JA, Buttner U, Cohen B. Baumgartner G. Vertical gaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus. Brain 1982;105:125-149. http://www.ncbi.nlm.nih.gov/pubmed/7066670 7. Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw JJ, Lyon-Caen O. Paramedian thalamic and midbrain infarcts; clinical and neuropathological study. Ann Neurol 1981;10:127-148. http://www.ncbi.nlm.nih.gov/pubmed/7283400 8. Halmagyi GM, Brandt T, Dieterich M, Curthoys IS, Stark RJ, Hoyt WF. Tonic contraversive Ocular tilt reaction due to unilateral meso-diencephalic lesion. Neurology 1990;40:1503-1509. http://www.ncbi.nlm.nih.gov/pubmed/2215939 9. Hommel M., Bogousslavsky J. The spectrum of vertical gaze palsy following unilateral brainstem stroke. Neurology 1991;41:1229-1234. http://www.ncbi.nlm.nih.gov/pubmed/1866011 10. Percheron G. Les artères du thalamus humain. II Artères et territores thalamiques paramédians de l'artère basilaire communicante. Rev Neurol 1976;132:309-324. 11. Pierrot-Deselligny C. Chain F, Gray F, Serdaru M, Escourolle R, Lhermitte F. Parinaud's syndrome: electrooculographic and anatomical analyses of six vascular cases with deductions about vertical gaze organization in the premotor structures. Brain 1982;105:667-696. http://www.ncbi.nlm.nih.gov/pubmed/7139250 12. Ranalli PJ, Sharpe JA, Fletcher WA. Palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations. Neurol 1988; 38(1):114-122. http://www.ncbi.nlm.nih.gov/pubmed/3336442 13. Seifert T, Enzinger C, Ropele S, Storch MK, Fazekas F. Midbrain ischemia presenting as vertical gaze palsy; value of diffusion-weighted magnetic resonance imaging. Cerebrovasc Dis 2004;18:3-7. http://www.ncbi.nlm.nih.gov/pubmed/15159614 14. Trojanowski JQ, Wray SH. Vertical gaze ophthalmoplegia: selective paralysis of downgaze. Neurology 1980;30:605-610. http://www.ncbi.nlm.nih.gov/pubmed/7189837MTemspverticalgazepals
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Bilateral Sixth Nerve Palsy
Spencer S. Eccles Health Sciences Library University of Utah, 1997Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Bilateral Sixth Nerve Palsy; Bilateral Esotropia; Paraneoplastic Opsoclonus/FlutterDouble Vision and ataxiaThis patient is a 62 year old woman with a six month history of double vision and difficulty walking. In August 1996, she first noted her right upper eyelid twitching followed by dizziness, nausea and vomiting. Soon after her voice became "shaky" and she experienced mild difficulty walking. She consulted her primary care physician and was prescribed Zoloft for depression. In November 1996, she developed double vision, and increasing unsteadiness walking. In December 1996, she consulted a neurologist. Brain MRI at an outside hospital reported to be normal In January 1997, she was admitted to Massachusetts General Hospital. Past History: Significant for right breast cancer in 1986, status post lumpectomy and radiation therapy. Family History: Negative for neurologic disease Neurological examination: Normal cognitive function Mild dysarthria and tremulous voice Spontaneous myoclonus and bilateral hand tremors Mild left hemiparesis with hyperreflexia and extensor plantar response Right flexor plantar response Bilateral limb ataxia and gait ataxia Neuro-ophthalmological examination: Visual acuity 20/20 OU Visual fields, pupils and fundus examination no abnormality Ocular Motility: • Intermittent opsoclonus with multivectorial conjugate saccades without an intersaccadic interval and • Ocular flutter with horizontal back to back saccades in central gaze • Esotropia OS > OD • Weakness of abduction OS - left sixth nerve palsy • Weakness of adduction OS • Weakness of abduction OD - right sixth nerve palsy • Full upgaze with upbeat nystagmus • Full downgaze with no nystagmus • Pursuit movements normal. Testing for Ocular Dysmetria show slow refixation saccades. No Dysmetria. Diagnosis: Paraneoplastic cerebellar syndrome with opsoclonus/flutter. 1/27/97 Brain MRI: The following sequences were obtained: Axial FLAIR, T1, FSE T2, Diffusion weighted images and post gadolinium. The study showed areas of T2 and FLAIR hyperintensity involving the tegmen and extending cranially to the midbrain adjacent to the midline and just inferior to the cerebellar peduncle. Also noted were areas of FLAIR and T2 hyperintensity within the corona radiata and centrum semiovale bilaterally, left greater than right. Similar signal abnormalities were seen within the right putamen and globus pallidus. Impression: Diffuse demyelinating process consistent with a paraneoplastic syndrome. Lumbar Puncture: Cerebrospinal fluid protein 36 mg/dl Sugar 68 mg/dl 136 RBC 12 WBC 95% lymphs 4% monocytes Positive for oligoclonal bands Cytology was negative for malignant cells twice Chest/abdomen/pelvic CT Normal Bone scan and bone marrow biopsy: Normal Mammogram: Bilateral mammogram Cluster of microcalcifications in the subareolar region of the lateral aspect of the left breast suspicious for intraductal carcinoma. Procedure: A needle guided left breast biopsy Pathology: Intraductal adenocarcinoma in situ in the left breast. The primary breast cancer being in the right breast. Paraneoplastic Markers: CSF and serum were sent to Dr. Posner at the Memorial Sloane Kettering Cancer Center for antibody studies (Anti-Ri, Anti-Yo). No antibodies were detected. Ri Autoantibody Test - Negative Anti-Ri is a highly specific antineuronal antibody that reacts with nuclei of neurons in the central nervous system. The presence of anti-Ri antibody identifies the subset of patients with paraneoplastic ataxia and opsoclonus who suffer from breast or other gynecological cancer. The antibody when present is a useful marker for this type of underlying malignancy. The relative amount of anti-Ri was found to be always higher in CSF than in serum. 1. Anderson NE et al. Ann Neurol 1988;24:559-567 2. Budde-Steffen C. et al. Ann Neurol 1988;23:528-531. 3. Luque A. et al. Ann Neurol 1989;26:178 (Abstract) All diagnostic antibody tests should be considered within the context of clinical findings. 1. Dalmau et al. 1992 Medicine 71:2;59-72. Diagnosis: 1. Paraneoplastic opsoclonus/Ocular flutter 2. Paraneoplastic cerebellar syndrome 3. Paraneoplastic brainstem encephalitis 4. Bilateral sixth nerve palsy 5. Intraductal adenocarcinoma in situ left breast Surgical resection of the intraductal adenocarcinoma in situ was done. Therapy: Ten days of IV solumedrol 1 gm per day Five day course of IV IgG For an overview of paraneoplastic opsoclonus/flutter review: ID931-1 Paraneoplastic opsoclonus/CA breast, ID936-7 Paraneoplastic Ocular flutter/CA lung. Hospital Course: Over a period of ten days the opsoclonus and flutter completely resolved and there was significant improvement in her ophthalmoplegia. The left eye regained almost full abduction and the right eye was able to cross the midline looking right. The spontaneous myoclonus stopped, hand tremors waxed and waned but overall improved, and the gait instability was markedly improved. She was able to walk in her room without a walker and in the hallway with a wheeled walker. She was hospitalized for three weeks and then discharged to a rehabilitation hospital. Discharge medication: Prednisone 10 mg daily, three times a day and on a tapering dose to stop after two weeks. The patient was followed by the neuro-oncology team.This 62 year old woman with paraneoplastic opsoclonus/flutter and diplopia due to bilateral sixth nerve palsy describes the visual disturbance of oscillopsia. At the time the video was made she had no opsoclonus/flutter. The eyes show: • Esotropia OS > OD • Weakness of abduction OS - left sixth nerve palsy • Weakness of abduction OD - right sixth nerve palsy • Impaired adduction OS • Full upgaze with upbeat nystagmus • Full downgaze with no nystagmus • Pursuit movements normal. Testing for Ocular Dysmetria show slow refixation saccades. No Dysmetria. In addition this patient had • Bilateral ataxia on finger/nose test and heel-knee-shin • Loss of rhythm hand tapping • Gait ataxia Ocular flutter and flutter Dysmetria are the major diagnostic signs. • Intermittent epochs of Ocular flutter - horizontal back-to-back saccadic oscillations without an intersaccadic interval. • Flutter Dysmetria most evident when the eyes make voluntary saccadic movements to the left Occasionally the amplitude of flutter is very small - microflutter, and the oscillations only detected with an ophthalmoscope or eye movement recordings. (6). Ocular flutter is often associated with paraneoplastic opsoclonus. Comment Dr. Zee (DZ), March 2007 SHW: David, I neglected to test for Ocular flutter under closed lids by asking the patient to look to the right and back to center and to the left and back to center. Would I expect to see flutter with eyes closed? DZ: Good question. This would seem to be very likely since eye closure shuts off the pause cells, and flutter itself can often be triggered by making a saccade, even in the light.Neuroimaging studies are unavailable in this case. Illustrative brain MRI scans in another patient with paraneoplastic opsoclonus/Ocular flutter are shown here. Axial FLAIR shows hyperintensity in both cerebellar hemispheres. Axial FLAIR through the mid-pons shows striking signal abnormality in the dorsal pons and cerebellar hemispheres. Axial FLAIR scan through the upper pons shows paraneoplastic brainstem multifocal hyperintensities consistent with encephalitis. (Courtesy of Anne Osborn, M.D.)Paraneoplastic opsoclonus/Ocular flutter is thought to be humorally mediated, and antibodies to diverse auto-antigens have been reported, but most patients are seronegative as in this case. The antineural antibodies associated with opsoclonus include Anti-Ri, Anti-Hu, Anti-Yo, Anti-Mal, and Anti-amphyphisin antibodies. With regard to opsoclonus (OC), it is not known whether OC is a cerebellar or brainstem disorder. (Review case ID931-1 the index case for the Anti-Ri antibody and ID936-7 Paraneoplastic Ocular flutter). Cerebellum: Wong et al have suggested, on theoretical grounds, that the deep cerebellar nuclei should be activated in patients with opsoclonus. (9) Helmchen et al (7) assessed this hypothesis with fMRI in two patients with opsoclonus and compared them with healthy subjects. They used three-dimensional (3D) scleral search coil recordings to characterize the pathologic eye oscillations. Fortuitously, both patients showed a decrease of or no OC with the eyes closed, so fMRI signals under two conditions (open eyes with OC vs closed eyes without OC) could be compared. A comparison of these two states revealed neither cerebellar vermal nor brainstem activation but showed, for the first time, bilateral functional activation of the deep cerebellar fastigial nuclei. This result supports Wong et al's recent hypothesis that OC results from a disinhibition of the fastigial Ocular motor region (FOR). FOR contains saccade-related neurons that augment the ongoing discharge of pontine excitory and inhibitory burst neurons. Because the cerebellar Ocular motor vermis physiologically inhibits FOR, the authors concluded that the absence of vermal activation during OC may reflect a cause of OC. Brainstem: Glycine has been identified as the neurotransmitter of omnipause neurons and poisoning with a glycine antagonist, strychnine, is reported to produce opsoclonus and myoclonus. Zee postulates that an immune-mediated Glycine Channelopathy affecting the membrane of omnipause cells may be the underlying mechanism for Ocular flutter and opsoclonus and that it may be possible that membrane-stabilizing drugs may have a therapeutic role for flutter and opsoclonus in the future. (Personal communication, 2007) (For further discussion see ref 8).Intraductal adenocarcinoma of the breastImmune modulation - intravenous IgG1. Alderson LM. Neurologic complications of breast cancer. In: Office Practice of Neurology 2nd Edition. Eds. Samuels MA, Feske SK. Churchill Livingston, 2003; 184:1181-1186. 2. Anderson NE. Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration: clinical-immunological correlations. Ann Neurol 1988;24:559-567. http://www.ncbi.nlm.nih.gov/pubmed/3239956 3. Bataller L, Dalmau J. Paraneoplastic Neurologic Syndromes: Approaches to Diagnosis and Treatment. Semin Neurol 2003;23:215-224. http://www.ncbi.nlm.nih.gov/pubmed/12894387 4. Budde-Steffen C, Anderson NE, Rosenblum MK, Graus F., Ford, D, Synek, BJL, Wray, SH, Posner JB. An anti-neuronal autoantibody in paraneoplastic opsoclonus. Ann Neurol 1988;23:528-531. http://www.ncbi.nlm.nih.gov/pubmed/3389761 5. Cogan DG. Ocular Dysmetria, flutter-like oscillations of the eyes and opsoclonus. Arch. Ophthalmol 1954;51:318. http://www.ncbi.nlm.nih.gov/pubmed/13123617 7. Helmchen C, Rambold H, Sprenger A, Erdmann C, Binkofski F. Cerebellar activation in opsoclonus: An fMRI study. Neurology 2003;61:412-415. http://www.ncbi.nlm.nih.gov/pubmed/12913213 8. Leigh RJ, Zee DS. Diagnosis of Pheripheral Ocular Motor Palsies and Strabismus Chp 9:385-474. In The Neurology of Eye Movements. 4th Ed. Oxford University Press, New York 2006. 9. Wong AM, Musallam S, Tomlinson RD, Shannon P, Sharpe JA. Opsoclonus in three dimensions: oculographic, neuropathologic and modeling correlates. J Neurol Sci 2001;189:71-81. http://www.ncbi.nlm.nih.gov/pubmed/1153523
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Benign Neonatal Ocular Flutter
Spencer S. Eccles Health Sciences Library University of Utah, 1994Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Ocular FlutterJiggling EyesShortly after birth, this baby was noted to have "jiggling eyes" by his mother. He was in good general health and neurologically intact. Cogan and I saw the baby and Cogan made the diagnosis of neonatal Ocular flutter. In 1954 Cogan first used the term "Ocular flutter" to describe a rare disorder of horizontal eye movements characterized by rapid bursts of synchronous back-to-back horizontal oscillatory movements usually seen in the primary position of gaze. Since then, there have been over 50 reports, usually single cases or small series, linking the phenomenon to a wide variety of brainstem and cerebellar conditions, e.g. post enteroviral infection, cerebral malaria, cyclosporine treatment and meningitis, but perhaps most frequently associated with parainfectious states or, with opsoclonus, as a paraneoplastic manifestation of occult malignancy. Benign neonatal Ocular flutter should only be diagnosed when all other potential etiologies have been ruled out by appropriate investigations.This baby has benign neonatal Ocular flutter. Watch this baby's eyes carefully for very short bursts of very fast conjugate horizontal back-to-back saccades without an intersaccadic interval. This tape is an excellent example of a case of benign neonatal Ocular flutter. At this time, bursts of flutter were less frequent and shorter in duration than on his initial visit, three weeks previous to this recording. Ocular flutter resolved completely over the next six weeks. Idiopathic opsoclonus can however occur as a transient phenomenon in an otherwise normal infant.1. Ashe J, Hain TC, Zee DS, Schatz NJ. Microsaccadic flutter. Brain 1991;114:461-472. http://www.ncbi.nlm.nih.gov/pubmed/2004251 2. Cogan DG. Ocular Dysmetria: flutter like oscillations of the eyes and opsoclonus. Arch Ophthalmol 1954;51:318-335. http://www.ncbi.nlm.nih.gov/pubmed/13123617 3. Dyken P, Kolar O. Dancing eye dancing feet: Infantile polymyoclonia. Brain 1968; 91:305-320. http://www.ncbi.nlm.nih.gov/pubmed/5721932 4. Hankey GJ, Sadka M. Ocular flutter postural body tremulousness and CSF pleocytosis: a rare postinfectious syndrome. J Neurol Neurosurg Psychiatry 1987;50:1235-1236. http://www.ncbi.nlm.nih.gov/pubmed/3668576 5. Hoyt CS, Mousel DK, Weber AA. Transient supranuclear disorders of gaze in healthy neonates. Am J Ophthalmol 1980;89:708-711. http://www.ncbi.nlm.nih.gov/pubmed/7377270 6. Hoyt CS, Gelbart SS. Vertical mystagmus in infants with congenital Ocular abnormalities. Ophthalmic Pediatr Genet 1984;4:155-162. http://www.ncbi.nlm.nih.gov/pubmed/6443616 7. Kinsbourne M. Myoclonic encephalopathy of infants. J Neurol Neurosurg Psychiatry 1962;25:2712-276. http://www.ncbi.nlm.nih.gov/pubmed/21610907 8. Kuban KC, Ephros MA, Freeman RL, Laffell LB, Bresnan MJ. Syndrome of opsoclonus-myoclonus caused by Coxsackie B3 infection. Ann Neurol 1983;13:69-71. http://www.ncbi.nlm.nih.gov/pubmed/6299176 9. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusion. Chp 10:475-558. In: The Neurology of Eye Movements, Fourth Edition. Oxford University Press, NY. 2006. 10. Orzechowski K, Walichiewicz T. Przypadek operowanej torbieli srodpajeczy mozdika (operated cyst of the cerebellum) Licowski Tygodnik Lekurski 1913;18:219-227. 11. Pranzatelli MR, Tate ED, Travelstead AL, Longee D. Immunologic and clinical responses to rituximab in a child with opsoclonus-myoclonus syndrome. Pediatrics 2005;115:115-119. http://www.ncbi.nlm.nih.gov/pubmed/15601813 12. Shawkat FS, Harris CM, Wilson J, Taylor DSI. Eye movements in children with opsoclonus. Neuropaediatrics 1993;24:218-223. http://www.ncbi.nlm.nih.gov/pubmed/8232781 13. Wiest G, Safoschnik G, Schnaberth G, Mueller C. Ocular flutter and truncal ataxia may be associated with enterovirus infection. J Neurology 1997, 244:288-292. http://www.ncbi.nlm.nih.gov/pubmed/917815
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Upbeat_Nystagmus
Spencer S. Eccles Health Sciences Library University of Utah, 1Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:The patient, a 36 year old Italian, presented in October 1967, at the age of 27, with acute dizziness and ataxia. He was evaluated in Rome. A pneumoencephalogram showed hydrocephalus, attributed to arachnoiditis, and a ventriculo-atrial shunt was placed. Three months post shunt placement he had a return of dizziness and ataxia accompanied by daily bi-occipital headache, diplopia, clumsiness and weakness of the left arm. In January 1968, he was readmitted and a large tumor of the left cerebellar hemisphere with invasion of the vermis was biopsied. A diagnosis of glioblastoma multiforme was made. He was treated with radiation therapy. Post operatively his major deficits were Ocular Dysmetria, left limb and gait ataxia. In 1970 he immigrated to the US. In 1971 he was referred to Dr. William Sweet, Chief of Neurosurgery at the Massachusetts General Hospital (MGH) with increasing gait ataxia and oscillopsia. Neurological examination: Cranial nerves intact (apart from the eye movements) Motor strength normal Decreased tone in the left extremities Reflexes 2+ throughout with flexor/plantar responses. Coordination: ataxia left extremities Gait ataxia, Romberg negative. Sensory examination normal. Neuro-ophthalmological examination: Visual acuity 20/20 OU Visual fields and pupils normal Fundus exam showed bilateral optic disc drusen Eye movements: •Upbeat nystagmus in primary gaze, increased on up gaze •Square wave jerks •Horizontal gaze evoked nystagmus left > right •Full vertical gaze •Upbeat nystagmus on upgaze •No nystagmus on downgaze •Pursuit, (horizontal and vertical) smooth to a very slow target, markedly saccadic to a fast target •Convergence normal •Marked saccadic hypermetria Right gaze to center overshoot (hypermetria) taking the eyes almost fully to the left Left gaze to center hypermetria taking the eyes almost fully to the right Upgaze to center hypermetria Downgaze to center hypermetria CT scan: In the region of the vermis and the medial portion of the left hemisphere there was an area of high absorption with contrast enhancement involving the cerebellar vermis and medial left cerebellar hemisphere with an apparent associated cystic component consistent with recurrent tumor. Cerebral Arteriogram: A cerebral arteriogram confirmed a highly vascular tumor of the inferior portion of the midline of the cerebellum, bulging into the fourth ventricle. Pathology: The slides from the original biopsy were obtained from Rome and reviewed by Dr E. P. Richardson, Chief of Neuropathology at the MGH. Diagnosis: A high-grade astrocytoma grade 3-4. Surgical procedure: A posterior fossa craniotomy was performed. To access the tumor, the most inferior aspect of the vermis was split to reach the roof of the 4th ventricle. In so doing, a well demarcated tumor nodule was found extending to both sides of the cerebellum, mostly to the left side. It was possible to separate the superior most aspect of the tumor easily from the 4th ventricle. Several small branches of the posterior inferior cerebellar arteries had to be divided to devascularize the tumor which was then gently dissected away from the floor of the 4th ventricle. At the end, the surgeon felt he had as close to a grossly total removal of the tumor as was possible and no visible tumor was left behind. Post operative status: The patient made a good post-operative recovery and was able to walk with an elbow crutch. He continued to be followed by neurosurgery until he was 66 years of age. During that time he had required a shunt revision on two occasions and therapy for an episode of meningitis/cerebritis. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/28
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Supranuclear_Paralysis_of_Vertical_Gaze
Spencer S. Eccles Health Sciences Library University of Utah, 1Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:This case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2007. The patient is a healthy, 36 year old Lieutenant Commander in the Coast Guard who was last seen perfectly well at 2 a.m. on the day of admission. He awoke in the morning around 9 a.m. having over slept - a rare event for him and noticed immediately that his vision was "all askew" due to vertical diplopia. On his way to work he felt tilted to the left and a little off balance tending to veer to the left. His left face was slightly drooped and the left arm and leg were clumsy. When he arrived at the office he was unable to type. The fingers of his left hand were clumsy and failed to hit the keys accurately. He complained of fatigue and attributed this to working almost non-stop for two weeks at his computer to design a software program. Symptomatic Inquiry: Negative for headache, vertigo, speech disturbance, chest pain, shortness of breath or palpitations. Family History: Negative for vascular and neurological disease. On examination: BP 110/60, heart rate 53, normal rhythm. General Neurological Examination: Mild left facial droop No pronator drift and normal motor strength throughout Intact coordination with no Dysmetria Deep tendon reflexes 1+ symmetric Plantar responses flexor Sensory system intact Ocular motility showed: A global supranuclear paralysis of vertical up and downgaze (only 15 degrees up, 5 degrees down from midposition) Vertical saccadic pursuit movements were limited over a similar range of eye movement. Convergence normal Horizontal gaze full Gaze evoked nystagmus to the right Horizontal gaze to the left, mild abduction weakness Ocular Dysmetria: Right gaze to center overshoot (hypermetric) Left gaze to center undershoot (hypometric) Vertical oculocephalic movements intact Bell's reflex intact (eyes deviated up under tightly closed lids). Additional eye signs: A left Ocular tilt reaction (OTR) is a central vestibular disorder involving the vertical vestibulo-Ocular reflex in the roll plane. The key to the diagnosis of an OTR is the combination of a 1.Lateral head tilt to the left in this case. 2.Hypertropia of the undermost eye, left eye, 3.Hypertropia of the contralateral right eye. 4.Fundus photography completes the triad and shows cyclodeviation of the eyes towards the head tilt (excyclotropia of the hypotropic eye; incyclotropia of the hypertropic eye). This patient did not complain of any perceptual tilt of the visual scene or crossed double images. Optokinetic nystagmus (OKN) with rotation of the stripes down, showed convergence retraction nystagmus as he attempted to look up to refixate the stripes. The pupils were abnormal - 5 mm OU with light/near dissociation. Investigations: Initially, there was concern for a diagnosis of endocarditis given the history of recent dental work and night sweats. Blood Studies: Complete blood count and erythrocyte sedimentation rate normal. Blood cultures x 3 negative. Hemocoagulable panel normal. Echocardiogram: A transthoracic and transesophageal echo revealed a patent foramen ovale with left to right shunting by Doppler. Chest x-ray and CT: Showed a right pulmonary embolus and lower lobe infarct. Abdominal/pelvic CT: Normal. Ultrasound and MRV of the lower extremities and pelvis revealed no deep vein thrombosis (DVT). CTA of the head showed: 1.Hyperdensity in the right anterior medial thalamus, consistent with infarction. 2.No hemodynamically significant lesion in the cervical or intracranial arterial circulation 3.Three mm. hypodense nodule in the posterior aspect of the left lobe of the thyroid gland Brain MRI perfusion imaging (7/16/07): 1.A DWI hyperintensity and corresponding ADC hypointensity in the right anterior medial thalamus extending into the right parasagittal midbrain adjacent to the red nucleus. (Figure 1) 2.A very faint FLAIR hyperintensity corresponding to the restricted diffusion image in the right thalamus. Diagnosis: Unilateral embolic infarction in the right anterior medial thalamus extending into the right mesencephalon adjacent to the red nucleus. Treatment: Warfarin sodium (Coumadin) 5 MG. p.o. q. p.m. Enoxaparin (Lovenox) 70 MG SC b.i.d. Discharge Diagnosis: 1.Discreet unilateral embolic infarct of the right paramedian thalamus and upper midbrain in the distribution of the posterior thalamo-subthalamic paramedian artery - the artery of Percheron (1). 2.A clinically silent right lower lobe pulmonary embolus. 3.Patent foramen ovale (PFO) with left to right shunting. Prognosis: The patient was advised that the prognosis for full recovery of his eye movements was excellent. On day 5, the vertical diplopia had resolved with complete resolution of the OTR and skew deviation. Two months later further recovery was noted with: 1.Full vertical gaze with slow vertical saccades most marked on up gaze 2.Looking down from a full upgaze position the eyes lateropulsed to the left or converged. 3.Beats of convergence nystagmus were provoked by a fast upward saccade and OKN with the stripes down. 4.He complained of persistent somnolence and had adopted the habit of setting 3 alarm clocks to wake him each morning. The patient returned 3 months after his acute stroke for closure of the PFO. On examination three weeks later, there was no change in his eye movements. He complained of excessive day time sleepiness. Brain MRI showed a rounded focus of T2 hyperintensity along the medial aspect of the right thalamus at the same location as a lesion with restricted diffusion on the prior brain MRI. (Figures 2A, B and C). See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/29
M Husain - One of the best experts on this subject based on the ideXlab platform.
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visually and memory guided saccades in a case of cerebellar saccadic Dysmetria
Journal of Neurology Neurosurgery and Psychiatry, 1994Co-Authors: R Kanayama, Alexander M. Bronstein, J Shallohoffmann, Peter Rudge, M HusainAbstract:Saccades under four specific test conditions (visually guided, visually remembered, vestibular remembered, and cervical remembered) were studied in a 38 year old man with Ocular Dysmetria due to an angioma of the dorsal cerebellar vermis. The aim of the study was to investigate if the saccadic disorder was specific to certain subsets of saccades elicited by different sensory modalities. The experiments showed that initial saccades were equally hypermetric in all four conditions and that final eye position was normal in all memory guided saccade tests. Eye movements differed after the initial saccade, however. Whereas corrective saccades were seen in most visually guided and visually remembered experiments, postsaccadic centripetal drifts were documented in non-visual (vestibular and cervical) remembered saccades. These results indicate that the cerebellar vermis modulates the amplitude of the initial saccade (pulse size of saccadic innervation) independently of the saccadic task. The finding that post-saccadic drift never occurred when saccades were programmed using visual positional information suggests that the dorsal vermis may participate in the process of pulse step integration of saccades elicited by memorised vestibulo-cervical information.
Professor Of Neurology Harvard Medical School - One of the best experts on this subject based on the ideXlab platform.
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Global Supranuclear Paralysis of Vertical Gaze
Spencer S. Eccles Health Sciences Library University of Utah, 2007Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Global Supranuclear Paralysis of Vertical Gaze; Absent Vertical Saccades and Pursuit Movements; Intact Convergence; Convergence Retraction Nystagmus; Ocular Dysmetria; Ocular Tilt Reaction; LateropulsionPowerPoint Presentations: Thalamic Stroke and Disordered Sleep: http://library.med.utah.edu/NOVEL/Wray/PPT/Thalamic_Stroke_and_Disordered_Sleep_guest_lecture.ppt Kenneth C. Sassower, M.D. Massachusetts General Hospital Supranuclear Vertical Gaze Palsy: http://library.med.utah.edu/NOVEL/Wray/PPT/Supranuclear_Paralysis_of_Vertical_Gaze.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical SchoolDouble vision; Gait imbalanceThis case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2007. The patient is a healthy, 36 year old Lieutenant Commander in the Coast Guard who was last seen perfectly well at 2 a.m. on the day of admission. He awoke in the morning around 9 a.m. having over slept - a rare event for him and noticed immediately that his vision was "all askew" due to vertical diplopia. On his way to work he felt tilted to the left and a little off balance tending to veer to the left. His left face was slightly drooped and the left arm and leg were clumsy. When he arrived at the office he was unable to type. The fingers of his left hand were clumsy and failed to hit the keys accurately. He complained of fatigue and attributed this to working almost non-stop for two weeks at his computer to design a software program. Symptomatic Inquiry: Negative for headache, vertigo, speech disturbance, chest pain, shortness of breath or palpitations. Family History: Negative for vascular and neurological disease. On examination: BP 110/60, heart rate 53, normal rhythm. General Neurological Examination: Mild left facial droop No pronator drift and normal motor strength throughout Intact coordination with no Dysmetria Deep tendon reflexes 1+ symmetric Plantar responses flexor Sensory system intact Ocular motility showed: A global supranuclear paralysis of vertical up and downgaze (only 15 degrees up, 5 degrees down from midposition) Vertical saccadic pursuit movements were limited over a similar range of eye movement. Convergence normal Horizontal gaze full Gaze evoked nystagmus to the right Horizontal gaze to the left, mild abduction weakness Ocular Dysmetria: Right gaze to center overshoot (hypermetric) Left gaze to center undershoot (hypometric) Vertical oculocephalic movements intact Bell's reflex intact (eyes deviated up under tightly closed lids). Additional eye signs: A left Ocular tilt reaction (OTR) is a central vestibular disorder involving the vertical vestibulo-Ocular reflex in the roll plane. The key to the diagnosis of an OTR is the combination of a 1. Lateral head tilt to the left in this case. 2. Hypertropia of the undermost eye, left eye, 3. Hypertropia of the contralateral right eye. 4. Fundus photography completes the triad and shows cyclodeviation of the eyes towards the head tilt (excyclotropia of the hypotropic eye; incyclotropia of the hypertropic eye). This patient did not complain of any perceptual tilt of the visual scene or crossed double images. Optokinetic nystagmus (OKN) with rotation of the stripes down, showed convergence retraction nystagmus as he attempted to look up to refixate the stripes. The pupils were abnormal - 5 mm OU with light/near dissociation. Investigations: Initially, there was concern for a diagnosis of endocarditis given the history of recent dental work and night sweats. Blood Studies: Complete blood count and erythrocyte sedimentation rate normal. Blood cultures x 3 negative. Hemocoagulable panel normal. Echocardiogram: A transthoracic and transesophageal echo revealed a patent foramen ovale with left to right shunting by Doppler. Chest x-ray and CT: Showed a right pulmonary embolus and lower lobe infarct. Abdominal/pelvic CT: Normal. Ultrasound and MRV of the lower extremities and pelvis revealed no deep vein thrombosis (DVT). CTA of the head showed: 1. Hyperdensity in the right anterior medial thalamus, consistent with infarction. 2. No hemodynamically significant lesion in the cervical or intracranial arterial circulation 3. Three mm. hypodense nodule in the posterior aspect of the left lobe of the thyroid gland Brain MRI perfusion imaging (7/16/07): 1. A DWI hyperintensity and corresponding ADC hypointensity in the right anterior medial thalamus extending into the right parasagittal midbrain adjacent to the red nucleus. (Figure 1) 2. A very faint FLAIR hyperintensity corresponding to the restricted diffusion image in the right thalamus. Diagnosis: Unilateral embolic infarction in the right anterior medial thalamus extending into the right mesencephalon adjacent to the red nucleus. Treatment: Warfarin sodium (Coumadin) 5 MG. p.o. q. p.m. Enoxaparin (Lovenox) 70 MG SC b.i.d. Discharge Diagnosis: 1. Discreet unilateral embolic infarct of the right paramedian thalamus and upper midbrain in the distribution of the posterior thalamo-subthalamic paramedian artery - the artery of Percheron (1). 2. A clinically silent right lower lobe pulmonary embolus. 3. Patent foramen ovale (PFO) with left to right shunting. Prognosis: The patient was advised that the prognosis for full recovery of his eye movements was excellent. On day 5, the vertical diplopia had resolved with complete resolution of the OTR and skew deviation. Two months later further recovery was noted with: 1. Full vertical gaze with slow vertical saccades most marked on up gaze 2. Looking down from a full upgaze position the eyes lateropulsed to the left or converged. 3. Beats of convergence nystagmus were provoked by a fast upward saccade and OKN with the stripes down. 4. He complained of persistent somnolence and had adopted the habit of setting 3 alarm clocks to wake him each morning. The patient returned 3 months after his acute stroke for closure of the PFO. On examination three weeks later, there was no change in his eye movements. He complained of excessive day time sleepiness. Brain MRI showed a rounded focus of T2 hyperintensity along the medial aspect of the right thalamus at the same location as a lesion with restricted diffusion on the prior brain MRI. (Figures 2A, B and C)The video clips of this case were taken with a hand held digital camera 4 days after the acute stroke. The first strip shows: Complete supranuclear paralysis of saccadic and pursuit upgaze with esodeviation of the left eye as he attempts to look up. Impaired conjugate downgaze and, on attempting to look down, the eyes converge. Convergence intact Vertical oculocephalic movements intact Bell's (upward deviation of the eyes under closed eyelids) intact A second clip taken 2 months later showed: Full up and downgaze with slow saccades on upgaze only and remarkable contraversive lateropulsion of the eyes to the left on full downgaze Vertical pursuit saccadic up and down Convergence intact Normal pupilsSee aboveThree neural structures in the midbrain reticular formation are involved in the generation of vertical eye movements: • Posterior commisure (PC) • Interstitial nucleus of Cajal (INC) and • Rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) In this case all three structures were damaged by the unilateral right paramedian thalamic midbrain infarct. Damage to the riMLF, and posterior commissure explains the global supranuclear paralysis of vertical gaze. Infarction of the right INC accounts for the left OTR. The infarct interrupted the pathways involved in vertical gaze just before they decussate producing an anatomically unilateral but functionally bilateral lesion. Involvement of the pretectal nuclei in the pupillary pathway, in the dorsum midbrain accounts for light-near dissociation of the pupils, and ischemia of the periaqueductal grey accounts for convergence retraction nystagmus. Literature review: Previous cases of bidirectional vertical gaze palsy from a unilateral right upper midbrain infarct have been reported. Alemdar M et al (2) reported a 47 year old woman who developed sudden complete loss of vertical saccades, smooth pursuit, and vestibular eye movements bilaterally. MRI revealed a unilateral midbrain infarct involving the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC) and spared the posterior commissure (PC). The lesion is presumed to have interrupted the pathways involved in vertical gaze just before they decussate, inducing an anatomically unilateral but functionally bilateral lesion. Previous reports of bidirectional vertical gaze palsy have shown lesions involving the PC or both riMLFs. Alemdar's case is the first to show that a unilateral lesion of the riMLF and the INC that spares the PC may cause complete bidirectional vertical gaze palsy. Ranalli PJ et al (12) quantified the vertical gaze defect in their patient by magnetic search coil oculography and documented the marked restriction of up and down saccades with preservation of only a 15 degree range of downward movement from midposition and a similar restriction of vertical pursuit movements. This patient had, in addition to a global vertical gaze palsy: 1. An inverted Bell's with the eyes deviating down on forced eye closure. 2. Seesaw nystagmus 3. Limited convergence 4. Limited oculocephalic movements 5. The pupil reflexes are not reported At autopsy a wedge-shaped area of infarction in the right midbrain tegmentum was found, situated dorsomedial to the rostral border of the red nucleus. Its caudal extent reached 1 mm below the level of the habenulopeduncular tract (tractus retroflexus of Meynert); it extended 10.5 mm rostrally, extending in two discreet bands in the medial thalamus, adjacent to the wall of the third ventricle. (Figure 1) The infarct destroyed the prerubral region containing the riMLF, the rostral one mm of the interstitial nucleus of Cajal (INC), the nucleus of Darkschewitsth and its invested fiber tracks, the ventral portion of the nucleus of the posterior commissure (NPCE) and parts of the dorsomedial and parafascicular thalamic nuclei. The posterior commissure, the left midbrain tegmentum, and Ocular motor nuclei were spared. The rest of the brainstem and cerebellum were also normal.Infarction destroying the prerubral region of the right midbrain and the dorsomedial and parafascicular region of the right thalamus.Unilateral Embolic Infarction in the distribution of the right posterior thalamus-subthalamic paramedian artery (Type 1) associated with a PFO.Anticoagulation followed by closure of a patent foramen ovale.1. Auerbach SH, DePiero TJ, Romanul F. Sylvian aqueduct syndrome caused by unilateral midbrain lesion. Ann Neurol 1982;11:91-94. http://www.ncbi.nlm.nih.gov/pubmed/7059132 2. Alemdar M, Kamaci MD, Budak F. Unilateral midbrain infarction causing upward and downward gaze palsy. J Neuro-Ophthalmol 2006;26:173-176. http://www.ncbi.nlm.nih.gov/pubmed/16966933 3. Brandt T, Dieterich M. Pathological eye-head coordination in roll: tonic Ocular tilt reaction in mesencephalic and medullary lesions. Brain 1987;110:694-666. http://www.ncbi.nlm.nih.gov/pubmed/3495315 4. Bhidayasiri R, Plant GT, Leigh RJ. A hypothetical scheme for the brainstem control of vertical gaze. Neurology 2000;54:1985-1993. http://www.ncbi.nlm.nih.gov/pubmed/10822441 5. Bogousslavsky J,Miklossy J, Regli F, Janzer R. Vertical gaze palsy and selective unilateral infarction of rostral interstitial nucleus of the medial longitudinal fasiculus (riMLF). J Neurol Neurosurg Psychiatry 1990;53:67-71. http://www.ncbi.nlm.nih.gov/pubmed/2303833 6. Buttner-Ennever JA, Buttner U, Cohen B. Baumgartner G. Vertical gaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus. Brain 1982;105:125-149. http://www.ncbi.nlm.nih.gov/pubmed/7066670 7. Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw JJ, Lyon-Caen O. Paramedian thalamic and midbrain infarcts; clinical and neuropathological study. Ann Neurol 1981;10:127-148. http://www.ncbi.nlm.nih.gov/pubmed/7283400 8. Halmagyi GM, Brandt T, Dieterich M, Curthoys IS, Stark RJ, Hoyt WF. Tonic contraversive Ocular tilt reaction due to unilateral meso-diencephalic lesion. Neurology 1990;40:1503-1509. http://www.ncbi.nlm.nih.gov/pubmed/2215939 9. Hommel M., Bogousslavsky J. The spectrum of vertical gaze palsy following unilateral brainstem stroke. Neurology 1991;41:1229-1234. http://www.ncbi.nlm.nih.gov/pubmed/1866011 10. Percheron G. Les artères du thalamus humain. II Artères et territores thalamiques paramédians de l'artère basilaire communicante. Rev Neurol 1976;132:309-324. 11. Pierrot-Deselligny C. Chain F, Gray F, Serdaru M, Escourolle R, Lhermitte F. Parinaud's syndrome: electrooculographic and anatomical analyses of six vascular cases with deductions about vertical gaze organization in the premotor structures. Brain 1982;105:667-696. http://www.ncbi.nlm.nih.gov/pubmed/7139250 12. Ranalli PJ, Sharpe JA, Fletcher WA. Palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations. Neurol 1988; 38(1):114-122. http://www.ncbi.nlm.nih.gov/pubmed/3336442 13. Seifert T, Enzinger C, Ropele S, Storch MK, Fazekas F. Midbrain ischemia presenting as vertical gaze palsy; value of diffusion-weighted magnetic resonance imaging. Cerebrovasc Dis 2004;18:3-7. http://www.ncbi.nlm.nih.gov/pubmed/15159614 14. Trojanowski JQ, Wray SH. Vertical gaze ophthalmoplegia: selective paralysis of downgaze. Neurology 1980;30:605-610. http://www.ncbi.nlm.nih.gov/pubmed/7189837MTemspverticalgazepals
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Bilateral Sixth Nerve Palsy
Spencer S. Eccles Health Sciences Library University of Utah, 1997Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Bilateral Sixth Nerve Palsy; Bilateral Esotropia; Paraneoplastic Opsoclonus/FlutterDouble Vision and ataxiaThis patient is a 62 year old woman with a six month history of double vision and difficulty walking. In August 1996, she first noted her right upper eyelid twitching followed by dizziness, nausea and vomiting. Soon after her voice became "shaky" and she experienced mild difficulty walking. She consulted her primary care physician and was prescribed Zoloft for depression. In November 1996, she developed double vision, and increasing unsteadiness walking. In December 1996, she consulted a neurologist. Brain MRI at an outside hospital reported to be normal In January 1997, she was admitted to Massachusetts General Hospital. Past History: Significant for right breast cancer in 1986, status post lumpectomy and radiation therapy. Family History: Negative for neurologic disease Neurological examination: Normal cognitive function Mild dysarthria and tremulous voice Spontaneous myoclonus and bilateral hand tremors Mild left hemiparesis with hyperreflexia and extensor plantar response Right flexor plantar response Bilateral limb ataxia and gait ataxia Neuro-ophthalmological examination: Visual acuity 20/20 OU Visual fields, pupils and fundus examination no abnormality Ocular Motility: • Intermittent opsoclonus with multivectorial conjugate saccades without an intersaccadic interval and • Ocular flutter with horizontal back to back saccades in central gaze • Esotropia OS > OD • Weakness of abduction OS - left sixth nerve palsy • Weakness of adduction OS • Weakness of abduction OD - right sixth nerve palsy • Full upgaze with upbeat nystagmus • Full downgaze with no nystagmus • Pursuit movements normal. Testing for Ocular Dysmetria show slow refixation saccades. No Dysmetria. Diagnosis: Paraneoplastic cerebellar syndrome with opsoclonus/flutter. 1/27/97 Brain MRI: The following sequences were obtained: Axial FLAIR, T1, FSE T2, Diffusion weighted images and post gadolinium. The study showed areas of T2 and FLAIR hyperintensity involving the tegmen and extending cranially to the midbrain adjacent to the midline and just inferior to the cerebellar peduncle. Also noted were areas of FLAIR and T2 hyperintensity within the corona radiata and centrum semiovale bilaterally, left greater than right. Similar signal abnormalities were seen within the right putamen and globus pallidus. Impression: Diffuse demyelinating process consistent with a paraneoplastic syndrome. Lumbar Puncture: Cerebrospinal fluid protein 36 mg/dl Sugar 68 mg/dl 136 RBC 12 WBC 95% lymphs 4% monocytes Positive for oligoclonal bands Cytology was negative for malignant cells twice Chest/abdomen/pelvic CT Normal Bone scan and bone marrow biopsy: Normal Mammogram: Bilateral mammogram Cluster of microcalcifications in the subareolar region of the lateral aspect of the left breast suspicious for intraductal carcinoma. Procedure: A needle guided left breast biopsy Pathology: Intraductal adenocarcinoma in situ in the left breast. The primary breast cancer being in the right breast. Paraneoplastic Markers: CSF and serum were sent to Dr. Posner at the Memorial Sloane Kettering Cancer Center for antibody studies (Anti-Ri, Anti-Yo). No antibodies were detected. Ri Autoantibody Test - Negative Anti-Ri is a highly specific antineuronal antibody that reacts with nuclei of neurons in the central nervous system. The presence of anti-Ri antibody identifies the subset of patients with paraneoplastic ataxia and opsoclonus who suffer from breast or other gynecological cancer. The antibody when present is a useful marker for this type of underlying malignancy. The relative amount of anti-Ri was found to be always higher in CSF than in serum. 1. Anderson NE et al. Ann Neurol 1988;24:559-567 2. Budde-Steffen C. et al. Ann Neurol 1988;23:528-531. 3. Luque A. et al. Ann Neurol 1989;26:178 (Abstract) All diagnostic antibody tests should be considered within the context of clinical findings. 1. Dalmau et al. 1992 Medicine 71:2;59-72. Diagnosis: 1. Paraneoplastic opsoclonus/Ocular flutter 2. Paraneoplastic cerebellar syndrome 3. Paraneoplastic brainstem encephalitis 4. Bilateral sixth nerve palsy 5. Intraductal adenocarcinoma in situ left breast Surgical resection of the intraductal adenocarcinoma in situ was done. Therapy: Ten days of IV solumedrol 1 gm per day Five day course of IV IgG For an overview of paraneoplastic opsoclonus/flutter review: ID931-1 Paraneoplastic opsoclonus/CA breast, ID936-7 Paraneoplastic Ocular flutter/CA lung. Hospital Course: Over a period of ten days the opsoclonus and flutter completely resolved and there was significant improvement in her ophthalmoplegia. The left eye regained almost full abduction and the right eye was able to cross the midline looking right. The spontaneous myoclonus stopped, hand tremors waxed and waned but overall improved, and the gait instability was markedly improved. She was able to walk in her room without a walker and in the hallway with a wheeled walker. She was hospitalized for three weeks and then discharged to a rehabilitation hospital. Discharge medication: Prednisone 10 mg daily, three times a day and on a tapering dose to stop after two weeks. The patient was followed by the neuro-oncology team.This 62 year old woman with paraneoplastic opsoclonus/flutter and diplopia due to bilateral sixth nerve palsy describes the visual disturbance of oscillopsia. At the time the video was made she had no opsoclonus/flutter. The eyes show: • Esotropia OS > OD • Weakness of abduction OS - left sixth nerve palsy • Weakness of abduction OD - right sixth nerve palsy • Impaired adduction OS • Full upgaze with upbeat nystagmus • Full downgaze with no nystagmus • Pursuit movements normal. Testing for Ocular Dysmetria show slow refixation saccades. No Dysmetria. In addition this patient had • Bilateral ataxia on finger/nose test and heel-knee-shin • Loss of rhythm hand tapping • Gait ataxia Ocular flutter and flutter Dysmetria are the major diagnostic signs. • Intermittent epochs of Ocular flutter - horizontal back-to-back saccadic oscillations without an intersaccadic interval. • Flutter Dysmetria most evident when the eyes make voluntary saccadic movements to the left Occasionally the amplitude of flutter is very small - microflutter, and the oscillations only detected with an ophthalmoscope or eye movement recordings. (6). Ocular flutter is often associated with paraneoplastic opsoclonus. Comment Dr. Zee (DZ), March 2007 SHW: David, I neglected to test for Ocular flutter under closed lids by asking the patient to look to the right and back to center and to the left and back to center. Would I expect to see flutter with eyes closed? DZ: Good question. This would seem to be very likely since eye closure shuts off the pause cells, and flutter itself can often be triggered by making a saccade, even in the light.Neuroimaging studies are unavailable in this case. Illustrative brain MRI scans in another patient with paraneoplastic opsoclonus/Ocular flutter are shown here. Axial FLAIR shows hyperintensity in both cerebellar hemispheres. Axial FLAIR through the mid-pons shows striking signal abnormality in the dorsal pons and cerebellar hemispheres. Axial FLAIR scan through the upper pons shows paraneoplastic brainstem multifocal hyperintensities consistent with encephalitis. (Courtesy of Anne Osborn, M.D.)Paraneoplastic opsoclonus/Ocular flutter is thought to be humorally mediated, and antibodies to diverse auto-antigens have been reported, but most patients are seronegative as in this case. The antineural antibodies associated with opsoclonus include Anti-Ri, Anti-Hu, Anti-Yo, Anti-Mal, and Anti-amphyphisin antibodies. With regard to opsoclonus (OC), it is not known whether OC is a cerebellar or brainstem disorder. (Review case ID931-1 the index case for the Anti-Ri antibody and ID936-7 Paraneoplastic Ocular flutter). Cerebellum: Wong et al have suggested, on theoretical grounds, that the deep cerebellar nuclei should be activated in patients with opsoclonus. (9) Helmchen et al (7) assessed this hypothesis with fMRI in two patients with opsoclonus and compared them with healthy subjects. They used three-dimensional (3D) scleral search coil recordings to characterize the pathologic eye oscillations. Fortuitously, both patients showed a decrease of or no OC with the eyes closed, so fMRI signals under two conditions (open eyes with OC vs closed eyes without OC) could be compared. A comparison of these two states revealed neither cerebellar vermal nor brainstem activation but showed, for the first time, bilateral functional activation of the deep cerebellar fastigial nuclei. This result supports Wong et al's recent hypothesis that OC results from a disinhibition of the fastigial Ocular motor region (FOR). FOR contains saccade-related neurons that augment the ongoing discharge of pontine excitory and inhibitory burst neurons. Because the cerebellar Ocular motor vermis physiologically inhibits FOR, the authors concluded that the absence of vermal activation during OC may reflect a cause of OC. Brainstem: Glycine has been identified as the neurotransmitter of omnipause neurons and poisoning with a glycine antagonist, strychnine, is reported to produce opsoclonus and myoclonus. Zee postulates that an immune-mediated Glycine Channelopathy affecting the membrane of omnipause cells may be the underlying mechanism for Ocular flutter and opsoclonus and that it may be possible that membrane-stabilizing drugs may have a therapeutic role for flutter and opsoclonus in the future. (Personal communication, 2007) (For further discussion see ref 8).Intraductal adenocarcinoma of the breastImmune modulation - intravenous IgG1. Alderson LM. Neurologic complications of breast cancer. In: Office Practice of Neurology 2nd Edition. Eds. Samuels MA, Feske SK. Churchill Livingston, 2003; 184:1181-1186. 2. Anderson NE. Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration: clinical-immunological correlations. Ann Neurol 1988;24:559-567. http://www.ncbi.nlm.nih.gov/pubmed/3239956 3. Bataller L, Dalmau J. Paraneoplastic Neurologic Syndromes: Approaches to Diagnosis and Treatment. Semin Neurol 2003;23:215-224. http://www.ncbi.nlm.nih.gov/pubmed/12894387 4. Budde-Steffen C, Anderson NE, Rosenblum MK, Graus F., Ford, D, Synek, BJL, Wray, SH, Posner JB. An anti-neuronal autoantibody in paraneoplastic opsoclonus. Ann Neurol 1988;23:528-531. http://www.ncbi.nlm.nih.gov/pubmed/3389761 5. Cogan DG. Ocular Dysmetria, flutter-like oscillations of the eyes and opsoclonus. Arch. Ophthalmol 1954;51:318. http://www.ncbi.nlm.nih.gov/pubmed/13123617 7. Helmchen C, Rambold H, Sprenger A, Erdmann C, Binkofski F. Cerebellar activation in opsoclonus: An fMRI study. Neurology 2003;61:412-415. http://www.ncbi.nlm.nih.gov/pubmed/12913213 8. Leigh RJ, Zee DS. Diagnosis of Pheripheral Ocular Motor Palsies and Strabismus Chp 9:385-474. In The Neurology of Eye Movements. 4th Ed. Oxford University Press, New York 2006. 9. Wong AM, Musallam S, Tomlinson RD, Shannon P, Sharpe JA. Opsoclonus in three dimensions: oculographic, neuropathologic and modeling correlates. J Neurol Sci 2001;189:71-81. http://www.ncbi.nlm.nih.gov/pubmed/1153523
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Benign Neonatal Ocular Flutter
Spencer S. Eccles Health Sciences Library University of Utah, 1994Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Ocular FlutterJiggling EyesShortly after birth, this baby was noted to have "jiggling eyes" by his mother. He was in good general health and neurologically intact. Cogan and I saw the baby and Cogan made the diagnosis of neonatal Ocular flutter. In 1954 Cogan first used the term "Ocular flutter" to describe a rare disorder of horizontal eye movements characterized by rapid bursts of synchronous back-to-back horizontal oscillatory movements usually seen in the primary position of gaze. Since then, there have been over 50 reports, usually single cases or small series, linking the phenomenon to a wide variety of brainstem and cerebellar conditions, e.g. post enteroviral infection, cerebral malaria, cyclosporine treatment and meningitis, but perhaps most frequently associated with parainfectious states or, with opsoclonus, as a paraneoplastic manifestation of occult malignancy. Benign neonatal Ocular flutter should only be diagnosed when all other potential etiologies have been ruled out by appropriate investigations.This baby has benign neonatal Ocular flutter. Watch this baby's eyes carefully for very short bursts of very fast conjugate horizontal back-to-back saccades without an intersaccadic interval. This tape is an excellent example of a case of benign neonatal Ocular flutter. At this time, bursts of flutter were less frequent and shorter in duration than on his initial visit, three weeks previous to this recording. Ocular flutter resolved completely over the next six weeks. Idiopathic opsoclonus can however occur as a transient phenomenon in an otherwise normal infant.1. Ashe J, Hain TC, Zee DS, Schatz NJ. Microsaccadic flutter. Brain 1991;114:461-472. http://www.ncbi.nlm.nih.gov/pubmed/2004251 2. Cogan DG. Ocular Dysmetria: flutter like oscillations of the eyes and opsoclonus. Arch Ophthalmol 1954;51:318-335. http://www.ncbi.nlm.nih.gov/pubmed/13123617 3. Dyken P, Kolar O. Dancing eye dancing feet: Infantile polymyoclonia. Brain 1968; 91:305-320. http://www.ncbi.nlm.nih.gov/pubmed/5721932 4. Hankey GJ, Sadka M. Ocular flutter postural body tremulousness and CSF pleocytosis: a rare postinfectious syndrome. J Neurol Neurosurg Psychiatry 1987;50:1235-1236. http://www.ncbi.nlm.nih.gov/pubmed/3668576 5. Hoyt CS, Mousel DK, Weber AA. Transient supranuclear disorders of gaze in healthy neonates. Am J Ophthalmol 1980;89:708-711. http://www.ncbi.nlm.nih.gov/pubmed/7377270 6. Hoyt CS, Gelbart SS. Vertical mystagmus in infants with congenital Ocular abnormalities. Ophthalmic Pediatr Genet 1984;4:155-162. http://www.ncbi.nlm.nih.gov/pubmed/6443616 7. Kinsbourne M. Myoclonic encephalopathy of infants. J Neurol Neurosurg Psychiatry 1962;25:2712-276. http://www.ncbi.nlm.nih.gov/pubmed/21610907 8. Kuban KC, Ephros MA, Freeman RL, Laffell LB, Bresnan MJ. Syndrome of opsoclonus-myoclonus caused by Coxsackie B3 infection. Ann Neurol 1983;13:69-71. http://www.ncbi.nlm.nih.gov/pubmed/6299176 9. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusion. Chp 10:475-558. In: The Neurology of Eye Movements, Fourth Edition. Oxford University Press, NY. 2006. 10. Orzechowski K, Walichiewicz T. Przypadek operowanej torbieli srodpajeczy mozdika (operated cyst of the cerebellum) Licowski Tygodnik Lekurski 1913;18:219-227. 11. Pranzatelli MR, Tate ED, Travelstead AL, Longee D. Immunologic and clinical responses to rituximab in a child with opsoclonus-myoclonus syndrome. Pediatrics 2005;115:115-119. http://www.ncbi.nlm.nih.gov/pubmed/15601813 12. Shawkat FS, Harris CM, Wilson J, Taylor DSI. Eye movements in children with opsoclonus. Neuropaediatrics 1993;24:218-223. http://www.ncbi.nlm.nih.gov/pubmed/8232781 13. Wiest G, Safoschnik G, Schnaberth G, Mueller C. Ocular flutter and truncal ataxia may be associated with enterovirus infection. J Neurology 1997, 244:288-292. http://www.ncbi.nlm.nih.gov/pubmed/917815
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Upbeat_Nystagmus
Spencer S. Eccles Health Sciences Library University of Utah, 1Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:The patient, a 36 year old Italian, presented in October 1967, at the age of 27, with acute dizziness and ataxia. He was evaluated in Rome. A pneumoencephalogram showed hydrocephalus, attributed to arachnoiditis, and a ventriculo-atrial shunt was placed. Three months post shunt placement he had a return of dizziness and ataxia accompanied by daily bi-occipital headache, diplopia, clumsiness and weakness of the left arm. In January 1968, he was readmitted and a large tumor of the left cerebellar hemisphere with invasion of the vermis was biopsied. A diagnosis of glioblastoma multiforme was made. He was treated with radiation therapy. Post operatively his major deficits were Ocular Dysmetria, left limb and gait ataxia. In 1970 he immigrated to the US. In 1971 he was referred to Dr. William Sweet, Chief of Neurosurgery at the Massachusetts General Hospital (MGH) with increasing gait ataxia and oscillopsia. Neurological examination: Cranial nerves intact (apart from the eye movements) Motor strength normal Decreased tone in the left extremities Reflexes 2+ throughout with flexor/plantar responses. Coordination: ataxia left extremities Gait ataxia, Romberg negative. Sensory examination normal. Neuro-ophthalmological examination: Visual acuity 20/20 OU Visual fields and pupils normal Fundus exam showed bilateral optic disc drusen Eye movements: •Upbeat nystagmus in primary gaze, increased on up gaze •Square wave jerks •Horizontal gaze evoked nystagmus left > right •Full vertical gaze •Upbeat nystagmus on upgaze •No nystagmus on downgaze •Pursuit, (horizontal and vertical) smooth to a very slow target, markedly saccadic to a fast target •Convergence normal •Marked saccadic hypermetria Right gaze to center overshoot (hypermetria) taking the eyes almost fully to the left Left gaze to center hypermetria taking the eyes almost fully to the right Upgaze to center hypermetria Downgaze to center hypermetria CT scan: In the region of the vermis and the medial portion of the left hemisphere there was an area of high absorption with contrast enhancement involving the cerebellar vermis and medial left cerebellar hemisphere with an apparent associated cystic component consistent with recurrent tumor. Cerebral Arteriogram: A cerebral arteriogram confirmed a highly vascular tumor of the inferior portion of the midline of the cerebellum, bulging into the fourth ventricle. Pathology: The slides from the original biopsy were obtained from Rome and reviewed by Dr E. P. Richardson, Chief of Neuropathology at the MGH. Diagnosis: A high-grade astrocytoma grade 3-4. Surgical procedure: A posterior fossa craniotomy was performed. To access the tumor, the most inferior aspect of the vermis was split to reach the roof of the 4th ventricle. In so doing, a well demarcated tumor nodule was found extending to both sides of the cerebellum, mostly to the left side. It was possible to separate the superior most aspect of the tumor easily from the 4th ventricle. Several small branches of the posterior inferior cerebellar arteries had to be divided to devascularize the tumor which was then gently dissected away from the floor of the 4th ventricle. At the end, the surgeon felt he had as close to a grossly total removal of the tumor as was possible and no visible tumor was left behind. Post operative status: The patient made a good post-operative recovery and was able to walk with an elbow crutch. He continued to be followed by neurosurgery until he was 66 years of age. During that time he had required a shunt revision on two occasions and therapy for an episode of meningitis/cerebritis. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/28
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Supranuclear_Paralysis_of_Vertical_Gaze
Spencer S. Eccles Health Sciences Library University of Utah, 1Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:This case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2007. The patient is a healthy, 36 year old Lieutenant Commander in the Coast Guard who was last seen perfectly well at 2 a.m. on the day of admission. He awoke in the morning around 9 a.m. having over slept - a rare event for him and noticed immediately that his vision was "all askew" due to vertical diplopia. On his way to work he felt tilted to the left and a little off balance tending to veer to the left. His left face was slightly drooped and the left arm and leg were clumsy. When he arrived at the office he was unable to type. The fingers of his left hand were clumsy and failed to hit the keys accurately. He complained of fatigue and attributed this to working almost non-stop for two weeks at his computer to design a software program. Symptomatic Inquiry: Negative for headache, vertigo, speech disturbance, chest pain, shortness of breath or palpitations. Family History: Negative for vascular and neurological disease. On examination: BP 110/60, heart rate 53, normal rhythm. General Neurological Examination: Mild left facial droop No pronator drift and normal motor strength throughout Intact coordination with no Dysmetria Deep tendon reflexes 1+ symmetric Plantar responses flexor Sensory system intact Ocular motility showed: A global supranuclear paralysis of vertical up and downgaze (only 15 degrees up, 5 degrees down from midposition) Vertical saccadic pursuit movements were limited over a similar range of eye movement. Convergence normal Horizontal gaze full Gaze evoked nystagmus to the right Horizontal gaze to the left, mild abduction weakness Ocular Dysmetria: Right gaze to center overshoot (hypermetric) Left gaze to center undershoot (hypometric) Vertical oculocephalic movements intact Bell's reflex intact (eyes deviated up under tightly closed lids). Additional eye signs: A left Ocular tilt reaction (OTR) is a central vestibular disorder involving the vertical vestibulo-Ocular reflex in the roll plane. The key to the diagnosis of an OTR is the combination of a 1.Lateral head tilt to the left in this case. 2.Hypertropia of the undermost eye, left eye, 3.Hypertropia of the contralateral right eye. 4.Fundus photography completes the triad and shows cyclodeviation of the eyes towards the head tilt (excyclotropia of the hypotropic eye; incyclotropia of the hypertropic eye). This patient did not complain of any perceptual tilt of the visual scene or crossed double images. Optokinetic nystagmus (OKN) with rotation of the stripes down, showed convergence retraction nystagmus as he attempted to look up to refixate the stripes. The pupils were abnormal - 5 mm OU with light/near dissociation. Investigations: Initially, there was concern for a diagnosis of endocarditis given the history of recent dental work and night sweats. Blood Studies: Complete blood count and erythrocyte sedimentation rate normal. Blood cultures x 3 negative. Hemocoagulable panel normal. Echocardiogram: A transthoracic and transesophageal echo revealed a patent foramen ovale with left to right shunting by Doppler. Chest x-ray and CT: Showed a right pulmonary embolus and lower lobe infarct. Abdominal/pelvic CT: Normal. Ultrasound and MRV of the lower extremities and pelvis revealed no deep vein thrombosis (DVT). CTA of the head showed: 1.Hyperdensity in the right anterior medial thalamus, consistent with infarction. 2.No hemodynamically significant lesion in the cervical or intracranial arterial circulation 3.Three mm. hypodense nodule in the posterior aspect of the left lobe of the thyroid gland Brain MRI perfusion imaging (7/16/07): 1.A DWI hyperintensity and corresponding ADC hypointensity in the right anterior medial thalamus extending into the right parasagittal midbrain adjacent to the red nucleus. (Figure 1) 2.A very faint FLAIR hyperintensity corresponding to the restricted diffusion image in the right thalamus. Diagnosis: Unilateral embolic infarction in the right anterior medial thalamus extending into the right mesencephalon adjacent to the red nucleus. Treatment: Warfarin sodium (Coumadin) 5 MG. p.o. q. p.m. Enoxaparin (Lovenox) 70 MG SC b.i.d. Discharge Diagnosis: 1.Discreet unilateral embolic infarct of the right paramedian thalamus and upper midbrain in the distribution of the posterior thalamo-subthalamic paramedian artery - the artery of Percheron (1). 2.A clinically silent right lower lobe pulmonary embolus. 3.Patent foramen ovale (PFO) with left to right shunting. Prognosis: The patient was advised that the prognosis for full recovery of his eye movements was excellent. On day 5, the vertical diplopia had resolved with complete resolution of the OTR and skew deviation. Two months later further recovery was noted with: 1.Full vertical gaze with slow vertical saccades most marked on up gaze 2.Looking down from a full upgaze position the eyes lateropulsed to the left or converged. 3.Beats of convergence nystagmus were provoked by a fast upward saccade and OKN with the stripes down. 4.He complained of persistent somnolence and had adopted the habit of setting 3 alarm clocks to wake him each morning. The patient returned 3 months after his acute stroke for closure of the PFO. On examination three weeks later, there was no change in his eye movements. He complained of excessive day time sleepiness. Brain MRI showed a rounded focus of T2 hyperintensity along the medial aspect of the right thalamus at the same location as a lesion with restricted diffusion on the prior brain MRI. (Figures 2A, B and C). See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/29
Unit For Neurovisual Disorders - One of the best experts on this subject based on the ideXlab platform.
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Global Supranuclear Paralysis of Vertical Gaze
Spencer S. Eccles Health Sciences Library University of Utah, 2007Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Global Supranuclear Paralysis of Vertical Gaze; Absent Vertical Saccades and Pursuit Movements; Intact Convergence; Convergence Retraction Nystagmus; Ocular Dysmetria; Ocular Tilt Reaction; LateropulsionPowerPoint Presentations: Thalamic Stroke and Disordered Sleep: http://library.med.utah.edu/NOVEL/Wray/PPT/Thalamic_Stroke_and_Disordered_Sleep_guest_lecture.ppt Kenneth C. Sassower, M.D. Massachusetts General Hospital Supranuclear Vertical Gaze Palsy: http://library.med.utah.edu/NOVEL/Wray/PPT/Supranuclear_Paralysis_of_Vertical_Gaze.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical SchoolDouble vision; Gait imbalanceThis case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2007. The patient is a healthy, 36 year old Lieutenant Commander in the Coast Guard who was last seen perfectly well at 2 a.m. on the day of admission. He awoke in the morning around 9 a.m. having over slept - a rare event for him and noticed immediately that his vision was "all askew" due to vertical diplopia. On his way to work he felt tilted to the left and a little off balance tending to veer to the left. His left face was slightly drooped and the left arm and leg were clumsy. When he arrived at the office he was unable to type. The fingers of his left hand were clumsy and failed to hit the keys accurately. He complained of fatigue and attributed this to working almost non-stop for two weeks at his computer to design a software program. Symptomatic Inquiry: Negative for headache, vertigo, speech disturbance, chest pain, shortness of breath or palpitations. Family History: Negative for vascular and neurological disease. On examination: BP 110/60, heart rate 53, normal rhythm. General Neurological Examination: Mild left facial droop No pronator drift and normal motor strength throughout Intact coordination with no Dysmetria Deep tendon reflexes 1+ symmetric Plantar responses flexor Sensory system intact Ocular motility showed: A global supranuclear paralysis of vertical up and downgaze (only 15 degrees up, 5 degrees down from midposition) Vertical saccadic pursuit movements were limited over a similar range of eye movement. Convergence normal Horizontal gaze full Gaze evoked nystagmus to the right Horizontal gaze to the left, mild abduction weakness Ocular Dysmetria: Right gaze to center overshoot (hypermetric) Left gaze to center undershoot (hypometric) Vertical oculocephalic movements intact Bell's reflex intact (eyes deviated up under tightly closed lids). Additional eye signs: A left Ocular tilt reaction (OTR) is a central vestibular disorder involving the vertical vestibulo-Ocular reflex in the roll plane. The key to the diagnosis of an OTR is the combination of a 1. Lateral head tilt to the left in this case. 2. Hypertropia of the undermost eye, left eye, 3. Hypertropia of the contralateral right eye. 4. Fundus photography completes the triad and shows cyclodeviation of the eyes towards the head tilt (excyclotropia of the hypotropic eye; incyclotropia of the hypertropic eye). This patient did not complain of any perceptual tilt of the visual scene or crossed double images. Optokinetic nystagmus (OKN) with rotation of the stripes down, showed convergence retraction nystagmus as he attempted to look up to refixate the stripes. The pupils were abnormal - 5 mm OU with light/near dissociation. Investigations: Initially, there was concern for a diagnosis of endocarditis given the history of recent dental work and night sweats. Blood Studies: Complete blood count and erythrocyte sedimentation rate normal. Blood cultures x 3 negative. Hemocoagulable panel normal. Echocardiogram: A transthoracic and transesophageal echo revealed a patent foramen ovale with left to right shunting by Doppler. Chest x-ray and CT: Showed a right pulmonary embolus and lower lobe infarct. Abdominal/pelvic CT: Normal. Ultrasound and MRV of the lower extremities and pelvis revealed no deep vein thrombosis (DVT). CTA of the head showed: 1. Hyperdensity in the right anterior medial thalamus, consistent with infarction. 2. No hemodynamically significant lesion in the cervical or intracranial arterial circulation 3. Three mm. hypodense nodule in the posterior aspect of the left lobe of the thyroid gland Brain MRI perfusion imaging (7/16/07): 1. A DWI hyperintensity and corresponding ADC hypointensity in the right anterior medial thalamus extending into the right parasagittal midbrain adjacent to the red nucleus. (Figure 1) 2. A very faint FLAIR hyperintensity corresponding to the restricted diffusion image in the right thalamus. Diagnosis: Unilateral embolic infarction in the right anterior medial thalamus extending into the right mesencephalon adjacent to the red nucleus. Treatment: Warfarin sodium (Coumadin) 5 MG. p.o. q. p.m. Enoxaparin (Lovenox) 70 MG SC b.i.d. Discharge Diagnosis: 1. Discreet unilateral embolic infarct of the right paramedian thalamus and upper midbrain in the distribution of the posterior thalamo-subthalamic paramedian artery - the artery of Percheron (1). 2. A clinically silent right lower lobe pulmonary embolus. 3. Patent foramen ovale (PFO) with left to right shunting. Prognosis: The patient was advised that the prognosis for full recovery of his eye movements was excellent. On day 5, the vertical diplopia had resolved with complete resolution of the OTR and skew deviation. Two months later further recovery was noted with: 1. Full vertical gaze with slow vertical saccades most marked on up gaze 2. Looking down from a full upgaze position the eyes lateropulsed to the left or converged. 3. Beats of convergence nystagmus were provoked by a fast upward saccade and OKN with the stripes down. 4. He complained of persistent somnolence and had adopted the habit of setting 3 alarm clocks to wake him each morning. The patient returned 3 months after his acute stroke for closure of the PFO. On examination three weeks later, there was no change in his eye movements. He complained of excessive day time sleepiness. Brain MRI showed a rounded focus of T2 hyperintensity along the medial aspect of the right thalamus at the same location as a lesion with restricted diffusion on the prior brain MRI. (Figures 2A, B and C)The video clips of this case were taken with a hand held digital camera 4 days after the acute stroke. The first strip shows: Complete supranuclear paralysis of saccadic and pursuit upgaze with esodeviation of the left eye as he attempts to look up. Impaired conjugate downgaze and, on attempting to look down, the eyes converge. Convergence intact Vertical oculocephalic movements intact Bell's (upward deviation of the eyes under closed eyelids) intact A second clip taken 2 months later showed: Full up and downgaze with slow saccades on upgaze only and remarkable contraversive lateropulsion of the eyes to the left on full downgaze Vertical pursuit saccadic up and down Convergence intact Normal pupilsSee aboveThree neural structures in the midbrain reticular formation are involved in the generation of vertical eye movements: • Posterior commisure (PC) • Interstitial nucleus of Cajal (INC) and • Rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) In this case all three structures were damaged by the unilateral right paramedian thalamic midbrain infarct. Damage to the riMLF, and posterior commissure explains the global supranuclear paralysis of vertical gaze. Infarction of the right INC accounts for the left OTR. The infarct interrupted the pathways involved in vertical gaze just before they decussate producing an anatomically unilateral but functionally bilateral lesion. Involvement of the pretectal nuclei in the pupillary pathway, in the dorsum midbrain accounts for light-near dissociation of the pupils, and ischemia of the periaqueductal grey accounts for convergence retraction nystagmus. Literature review: Previous cases of bidirectional vertical gaze palsy from a unilateral right upper midbrain infarct have been reported. Alemdar M et al (2) reported a 47 year old woman who developed sudden complete loss of vertical saccades, smooth pursuit, and vestibular eye movements bilaterally. MRI revealed a unilateral midbrain infarct involving the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC) and spared the posterior commissure (PC). The lesion is presumed to have interrupted the pathways involved in vertical gaze just before they decussate, inducing an anatomically unilateral but functionally bilateral lesion. Previous reports of bidirectional vertical gaze palsy have shown lesions involving the PC or both riMLFs. Alemdar's case is the first to show that a unilateral lesion of the riMLF and the INC that spares the PC may cause complete bidirectional vertical gaze palsy. Ranalli PJ et al (12) quantified the vertical gaze defect in their patient by magnetic search coil oculography and documented the marked restriction of up and down saccades with preservation of only a 15 degree range of downward movement from midposition and a similar restriction of vertical pursuit movements. This patient had, in addition to a global vertical gaze palsy: 1. An inverted Bell's with the eyes deviating down on forced eye closure. 2. Seesaw nystagmus 3. Limited convergence 4. Limited oculocephalic movements 5. The pupil reflexes are not reported At autopsy a wedge-shaped area of infarction in the right midbrain tegmentum was found, situated dorsomedial to the rostral border of the red nucleus. Its caudal extent reached 1 mm below the level of the habenulopeduncular tract (tractus retroflexus of Meynert); it extended 10.5 mm rostrally, extending in two discreet bands in the medial thalamus, adjacent to the wall of the third ventricle. (Figure 1) The infarct destroyed the prerubral region containing the riMLF, the rostral one mm of the interstitial nucleus of Cajal (INC), the nucleus of Darkschewitsth and its invested fiber tracks, the ventral portion of the nucleus of the posterior commissure (NPCE) and parts of the dorsomedial and parafascicular thalamic nuclei. The posterior commissure, the left midbrain tegmentum, and Ocular motor nuclei were spared. The rest of the brainstem and cerebellum were also normal.Infarction destroying the prerubral region of the right midbrain and the dorsomedial and parafascicular region of the right thalamus.Unilateral Embolic Infarction in the distribution of the right posterior thalamus-subthalamic paramedian artery (Type 1) associated with a PFO.Anticoagulation followed by closure of a patent foramen ovale.1. Auerbach SH, DePiero TJ, Romanul F. Sylvian aqueduct syndrome caused by unilateral midbrain lesion. Ann Neurol 1982;11:91-94. http://www.ncbi.nlm.nih.gov/pubmed/7059132 2. Alemdar M, Kamaci MD, Budak F. Unilateral midbrain infarction causing upward and downward gaze palsy. J Neuro-Ophthalmol 2006;26:173-176. http://www.ncbi.nlm.nih.gov/pubmed/16966933 3. Brandt T, Dieterich M. Pathological eye-head coordination in roll: tonic Ocular tilt reaction in mesencephalic and medullary lesions. Brain 1987;110:694-666. http://www.ncbi.nlm.nih.gov/pubmed/3495315 4. Bhidayasiri R, Plant GT, Leigh RJ. A hypothetical scheme for the brainstem control of vertical gaze. Neurology 2000;54:1985-1993. http://www.ncbi.nlm.nih.gov/pubmed/10822441 5. Bogousslavsky J,Miklossy J, Regli F, Janzer R. Vertical gaze palsy and selective unilateral infarction of rostral interstitial nucleus of the medial longitudinal fasiculus (riMLF). J Neurol Neurosurg Psychiatry 1990;53:67-71. http://www.ncbi.nlm.nih.gov/pubmed/2303833 6. Buttner-Ennever JA, Buttner U, Cohen B. Baumgartner G. Vertical gaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus. Brain 1982;105:125-149. http://www.ncbi.nlm.nih.gov/pubmed/7066670 7. Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw JJ, Lyon-Caen O. Paramedian thalamic and midbrain infarcts; clinical and neuropathological study. Ann Neurol 1981;10:127-148. http://www.ncbi.nlm.nih.gov/pubmed/7283400 8. Halmagyi GM, Brandt T, Dieterich M, Curthoys IS, Stark RJ, Hoyt WF. Tonic contraversive Ocular tilt reaction due to unilateral meso-diencephalic lesion. Neurology 1990;40:1503-1509. http://www.ncbi.nlm.nih.gov/pubmed/2215939 9. Hommel M., Bogousslavsky J. The spectrum of vertical gaze palsy following unilateral brainstem stroke. Neurology 1991;41:1229-1234. http://www.ncbi.nlm.nih.gov/pubmed/1866011 10. Percheron G. Les artères du thalamus humain. II Artères et territores thalamiques paramédians de l'artère basilaire communicante. Rev Neurol 1976;132:309-324. 11. Pierrot-Deselligny C. Chain F, Gray F, Serdaru M, Escourolle R, Lhermitte F. Parinaud's syndrome: electrooculographic and anatomical analyses of six vascular cases with deductions about vertical gaze organization in the premotor structures. Brain 1982;105:667-696. http://www.ncbi.nlm.nih.gov/pubmed/7139250 12. Ranalli PJ, Sharpe JA, Fletcher WA. Palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations. Neurol 1988; 38(1):114-122. http://www.ncbi.nlm.nih.gov/pubmed/3336442 13. Seifert T, Enzinger C, Ropele S, Storch MK, Fazekas F. Midbrain ischemia presenting as vertical gaze palsy; value of diffusion-weighted magnetic resonance imaging. Cerebrovasc Dis 2004;18:3-7. http://www.ncbi.nlm.nih.gov/pubmed/15159614 14. Trojanowski JQ, Wray SH. Vertical gaze ophthalmoplegia: selective paralysis of downgaze. Neurology 1980;30:605-610. http://www.ncbi.nlm.nih.gov/pubmed/7189837MTemspverticalgazepals
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Bilateral Sixth Nerve Palsy
Spencer S. Eccles Health Sciences Library University of Utah, 1997Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Bilateral Sixth Nerve Palsy; Bilateral Esotropia; Paraneoplastic Opsoclonus/FlutterDouble Vision and ataxiaThis patient is a 62 year old woman with a six month history of double vision and difficulty walking. In August 1996, she first noted her right upper eyelid twitching followed by dizziness, nausea and vomiting. Soon after her voice became "shaky" and she experienced mild difficulty walking. She consulted her primary care physician and was prescribed Zoloft for depression. In November 1996, she developed double vision, and increasing unsteadiness walking. In December 1996, she consulted a neurologist. Brain MRI at an outside hospital reported to be normal In January 1997, she was admitted to Massachusetts General Hospital. Past History: Significant for right breast cancer in 1986, status post lumpectomy and radiation therapy. Family History: Negative for neurologic disease Neurological examination: Normal cognitive function Mild dysarthria and tremulous voice Spontaneous myoclonus and bilateral hand tremors Mild left hemiparesis with hyperreflexia and extensor plantar response Right flexor plantar response Bilateral limb ataxia and gait ataxia Neuro-ophthalmological examination: Visual acuity 20/20 OU Visual fields, pupils and fundus examination no abnormality Ocular Motility: • Intermittent opsoclonus with multivectorial conjugate saccades without an intersaccadic interval and • Ocular flutter with horizontal back to back saccades in central gaze • Esotropia OS > OD • Weakness of abduction OS - left sixth nerve palsy • Weakness of adduction OS • Weakness of abduction OD - right sixth nerve palsy • Full upgaze with upbeat nystagmus • Full downgaze with no nystagmus • Pursuit movements normal. Testing for Ocular Dysmetria show slow refixation saccades. No Dysmetria. Diagnosis: Paraneoplastic cerebellar syndrome with opsoclonus/flutter. 1/27/97 Brain MRI: The following sequences were obtained: Axial FLAIR, T1, FSE T2, Diffusion weighted images and post gadolinium. The study showed areas of T2 and FLAIR hyperintensity involving the tegmen and extending cranially to the midbrain adjacent to the midline and just inferior to the cerebellar peduncle. Also noted were areas of FLAIR and T2 hyperintensity within the corona radiata and centrum semiovale bilaterally, left greater than right. Similar signal abnormalities were seen within the right putamen and globus pallidus. Impression: Diffuse demyelinating process consistent with a paraneoplastic syndrome. Lumbar Puncture: Cerebrospinal fluid protein 36 mg/dl Sugar 68 mg/dl 136 RBC 12 WBC 95% lymphs 4% monocytes Positive for oligoclonal bands Cytology was negative for malignant cells twice Chest/abdomen/pelvic CT Normal Bone scan and bone marrow biopsy: Normal Mammogram: Bilateral mammogram Cluster of microcalcifications in the subareolar region of the lateral aspect of the left breast suspicious for intraductal carcinoma. Procedure: A needle guided left breast biopsy Pathology: Intraductal adenocarcinoma in situ in the left breast. The primary breast cancer being in the right breast. Paraneoplastic Markers: CSF and serum were sent to Dr. Posner at the Memorial Sloane Kettering Cancer Center for antibody studies (Anti-Ri, Anti-Yo). No antibodies were detected. Ri Autoantibody Test - Negative Anti-Ri is a highly specific antineuronal antibody that reacts with nuclei of neurons in the central nervous system. The presence of anti-Ri antibody identifies the subset of patients with paraneoplastic ataxia and opsoclonus who suffer from breast or other gynecological cancer. The antibody when present is a useful marker for this type of underlying malignancy. The relative amount of anti-Ri was found to be always higher in CSF than in serum. 1. Anderson NE et al. Ann Neurol 1988;24:559-567 2. Budde-Steffen C. et al. Ann Neurol 1988;23:528-531. 3. Luque A. et al. Ann Neurol 1989;26:178 (Abstract) All diagnostic antibody tests should be considered within the context of clinical findings. 1. Dalmau et al. 1992 Medicine 71:2;59-72. Diagnosis: 1. Paraneoplastic opsoclonus/Ocular flutter 2. Paraneoplastic cerebellar syndrome 3. Paraneoplastic brainstem encephalitis 4. Bilateral sixth nerve palsy 5. Intraductal adenocarcinoma in situ left breast Surgical resection of the intraductal adenocarcinoma in situ was done. Therapy: Ten days of IV solumedrol 1 gm per day Five day course of IV IgG For an overview of paraneoplastic opsoclonus/flutter review: ID931-1 Paraneoplastic opsoclonus/CA breast, ID936-7 Paraneoplastic Ocular flutter/CA lung. Hospital Course: Over a period of ten days the opsoclonus and flutter completely resolved and there was significant improvement in her ophthalmoplegia. The left eye regained almost full abduction and the right eye was able to cross the midline looking right. The spontaneous myoclonus stopped, hand tremors waxed and waned but overall improved, and the gait instability was markedly improved. She was able to walk in her room without a walker and in the hallway with a wheeled walker. She was hospitalized for three weeks and then discharged to a rehabilitation hospital. Discharge medication: Prednisone 10 mg daily, three times a day and on a tapering dose to stop after two weeks. The patient was followed by the neuro-oncology team.This 62 year old woman with paraneoplastic opsoclonus/flutter and diplopia due to bilateral sixth nerve palsy describes the visual disturbance of oscillopsia. At the time the video was made she had no opsoclonus/flutter. The eyes show: • Esotropia OS > OD • Weakness of abduction OS - left sixth nerve palsy • Weakness of abduction OD - right sixth nerve palsy • Impaired adduction OS • Full upgaze with upbeat nystagmus • Full downgaze with no nystagmus • Pursuit movements normal. Testing for Ocular Dysmetria show slow refixation saccades. No Dysmetria. In addition this patient had • Bilateral ataxia on finger/nose test and heel-knee-shin • Loss of rhythm hand tapping • Gait ataxia Ocular flutter and flutter Dysmetria are the major diagnostic signs. • Intermittent epochs of Ocular flutter - horizontal back-to-back saccadic oscillations without an intersaccadic interval. • Flutter Dysmetria most evident when the eyes make voluntary saccadic movements to the left Occasionally the amplitude of flutter is very small - microflutter, and the oscillations only detected with an ophthalmoscope or eye movement recordings. (6). Ocular flutter is often associated with paraneoplastic opsoclonus. Comment Dr. Zee (DZ), March 2007 SHW: David, I neglected to test for Ocular flutter under closed lids by asking the patient to look to the right and back to center and to the left and back to center. Would I expect to see flutter with eyes closed? DZ: Good question. This would seem to be very likely since eye closure shuts off the pause cells, and flutter itself can often be triggered by making a saccade, even in the light.Neuroimaging studies are unavailable in this case. Illustrative brain MRI scans in another patient with paraneoplastic opsoclonus/Ocular flutter are shown here. Axial FLAIR shows hyperintensity in both cerebellar hemispheres. Axial FLAIR through the mid-pons shows striking signal abnormality in the dorsal pons and cerebellar hemispheres. Axial FLAIR scan through the upper pons shows paraneoplastic brainstem multifocal hyperintensities consistent with encephalitis. (Courtesy of Anne Osborn, M.D.)Paraneoplastic opsoclonus/Ocular flutter is thought to be humorally mediated, and antibodies to diverse auto-antigens have been reported, but most patients are seronegative as in this case. The antineural antibodies associated with opsoclonus include Anti-Ri, Anti-Hu, Anti-Yo, Anti-Mal, and Anti-amphyphisin antibodies. With regard to opsoclonus (OC), it is not known whether OC is a cerebellar or brainstem disorder. (Review case ID931-1 the index case for the Anti-Ri antibody and ID936-7 Paraneoplastic Ocular flutter). Cerebellum: Wong et al have suggested, on theoretical grounds, that the deep cerebellar nuclei should be activated in patients with opsoclonus. (9) Helmchen et al (7) assessed this hypothesis with fMRI in two patients with opsoclonus and compared them with healthy subjects. They used three-dimensional (3D) scleral search coil recordings to characterize the pathologic eye oscillations. Fortuitously, both patients showed a decrease of or no OC with the eyes closed, so fMRI signals under two conditions (open eyes with OC vs closed eyes without OC) could be compared. A comparison of these two states revealed neither cerebellar vermal nor brainstem activation but showed, for the first time, bilateral functional activation of the deep cerebellar fastigial nuclei. This result supports Wong et al's recent hypothesis that OC results from a disinhibition of the fastigial Ocular motor region (FOR). FOR contains saccade-related neurons that augment the ongoing discharge of pontine excitory and inhibitory burst neurons. Because the cerebellar Ocular motor vermis physiologically inhibits FOR, the authors concluded that the absence of vermal activation during OC may reflect a cause of OC. Brainstem: Glycine has been identified as the neurotransmitter of omnipause neurons and poisoning with a glycine antagonist, strychnine, is reported to produce opsoclonus and myoclonus. Zee postulates that an immune-mediated Glycine Channelopathy affecting the membrane of omnipause cells may be the underlying mechanism for Ocular flutter and opsoclonus and that it may be possible that membrane-stabilizing drugs may have a therapeutic role for flutter and opsoclonus in the future. (Personal communication, 2007) (For further discussion see ref 8).Intraductal adenocarcinoma of the breastImmune modulation - intravenous IgG1. Alderson LM. Neurologic complications of breast cancer. In: Office Practice of Neurology 2nd Edition. Eds. Samuels MA, Feske SK. Churchill Livingston, 2003; 184:1181-1186. 2. Anderson NE. Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration: clinical-immunological correlations. Ann Neurol 1988;24:559-567. http://www.ncbi.nlm.nih.gov/pubmed/3239956 3. Bataller L, Dalmau J. Paraneoplastic Neurologic Syndromes: Approaches to Diagnosis and Treatment. Semin Neurol 2003;23:215-224. http://www.ncbi.nlm.nih.gov/pubmed/12894387 4. Budde-Steffen C, Anderson NE, Rosenblum MK, Graus F., Ford, D, Synek, BJL, Wray, SH, Posner JB. An anti-neuronal autoantibody in paraneoplastic opsoclonus. Ann Neurol 1988;23:528-531. http://www.ncbi.nlm.nih.gov/pubmed/3389761 5. Cogan DG. Ocular Dysmetria, flutter-like oscillations of the eyes and opsoclonus. Arch. Ophthalmol 1954;51:318. http://www.ncbi.nlm.nih.gov/pubmed/13123617 7. Helmchen C, Rambold H, Sprenger A, Erdmann C, Binkofski F. Cerebellar activation in opsoclonus: An fMRI study. Neurology 2003;61:412-415. http://www.ncbi.nlm.nih.gov/pubmed/12913213 8. Leigh RJ, Zee DS. Diagnosis of Pheripheral Ocular Motor Palsies and Strabismus Chp 9:385-474. In The Neurology of Eye Movements. 4th Ed. Oxford University Press, New York 2006. 9. Wong AM, Musallam S, Tomlinson RD, Shannon P, Sharpe JA. Opsoclonus in three dimensions: oculographic, neuropathologic and modeling correlates. J Neurol Sci 2001;189:71-81. http://www.ncbi.nlm.nih.gov/pubmed/1153523
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Benign Neonatal Ocular Flutter
Spencer S. Eccles Health Sciences Library University of Utah, 1994Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:Ocular FlutterJiggling EyesShortly after birth, this baby was noted to have "jiggling eyes" by his mother. He was in good general health and neurologically intact. Cogan and I saw the baby and Cogan made the diagnosis of neonatal Ocular flutter. In 1954 Cogan first used the term "Ocular flutter" to describe a rare disorder of horizontal eye movements characterized by rapid bursts of synchronous back-to-back horizontal oscillatory movements usually seen in the primary position of gaze. Since then, there have been over 50 reports, usually single cases or small series, linking the phenomenon to a wide variety of brainstem and cerebellar conditions, e.g. post enteroviral infection, cerebral malaria, cyclosporine treatment and meningitis, but perhaps most frequently associated with parainfectious states or, with opsoclonus, as a paraneoplastic manifestation of occult malignancy. Benign neonatal Ocular flutter should only be diagnosed when all other potential etiologies have been ruled out by appropriate investigations.This baby has benign neonatal Ocular flutter. Watch this baby's eyes carefully for very short bursts of very fast conjugate horizontal back-to-back saccades without an intersaccadic interval. This tape is an excellent example of a case of benign neonatal Ocular flutter. At this time, bursts of flutter were less frequent and shorter in duration than on his initial visit, three weeks previous to this recording. Ocular flutter resolved completely over the next six weeks. Idiopathic opsoclonus can however occur as a transient phenomenon in an otherwise normal infant.1. Ashe J, Hain TC, Zee DS, Schatz NJ. Microsaccadic flutter. Brain 1991;114:461-472. http://www.ncbi.nlm.nih.gov/pubmed/2004251 2. Cogan DG. Ocular Dysmetria: flutter like oscillations of the eyes and opsoclonus. Arch Ophthalmol 1954;51:318-335. http://www.ncbi.nlm.nih.gov/pubmed/13123617 3. Dyken P, Kolar O. Dancing eye dancing feet: Infantile polymyoclonia. Brain 1968; 91:305-320. http://www.ncbi.nlm.nih.gov/pubmed/5721932 4. Hankey GJ, Sadka M. Ocular flutter postural body tremulousness and CSF pleocytosis: a rare postinfectious syndrome. J Neurol Neurosurg Psychiatry 1987;50:1235-1236. http://www.ncbi.nlm.nih.gov/pubmed/3668576 5. Hoyt CS, Mousel DK, Weber AA. Transient supranuclear disorders of gaze in healthy neonates. Am J Ophthalmol 1980;89:708-711. http://www.ncbi.nlm.nih.gov/pubmed/7377270 6. Hoyt CS, Gelbart SS. Vertical mystagmus in infants with congenital Ocular abnormalities. Ophthalmic Pediatr Genet 1984;4:155-162. http://www.ncbi.nlm.nih.gov/pubmed/6443616 7. Kinsbourne M. Myoclonic encephalopathy of infants. J Neurol Neurosurg Psychiatry 1962;25:2712-276. http://www.ncbi.nlm.nih.gov/pubmed/21610907 8. Kuban KC, Ephros MA, Freeman RL, Laffell LB, Bresnan MJ. Syndrome of opsoclonus-myoclonus caused by Coxsackie B3 infection. Ann Neurol 1983;13:69-71. http://www.ncbi.nlm.nih.gov/pubmed/6299176 9. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusion. Chp 10:475-558. In: The Neurology of Eye Movements, Fourth Edition. Oxford University Press, NY. 2006. 10. Orzechowski K, Walichiewicz T. Przypadek operowanej torbieli srodpajeczy mozdika (operated cyst of the cerebellum) Licowski Tygodnik Lekurski 1913;18:219-227. 11. Pranzatelli MR, Tate ED, Travelstead AL, Longee D. Immunologic and clinical responses to rituximab in a child with opsoclonus-myoclonus syndrome. Pediatrics 2005;115:115-119. http://www.ncbi.nlm.nih.gov/pubmed/15601813 12. Shawkat FS, Harris CM, Wilson J, Taylor DSI. Eye movements in children with opsoclonus. Neuropaediatrics 1993;24:218-223. http://www.ncbi.nlm.nih.gov/pubmed/8232781 13. Wiest G, Safoschnik G, Schnaberth G, Mueller C. Ocular flutter and truncal ataxia may be associated with enterovirus infection. J Neurology 1997, 244:288-292. http://www.ncbi.nlm.nih.gov/pubmed/917815
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Upbeat_Nystagmus
Spencer S. Eccles Health Sciences Library University of Utah, 1Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:The patient, a 36 year old Italian, presented in October 1967, at the age of 27, with acute dizziness and ataxia. He was evaluated in Rome. A pneumoencephalogram showed hydrocephalus, attributed to arachnoiditis, and a ventriculo-atrial shunt was placed. Three months post shunt placement he had a return of dizziness and ataxia accompanied by daily bi-occipital headache, diplopia, clumsiness and weakness of the left arm. In January 1968, he was readmitted and a large tumor of the left cerebellar hemisphere with invasion of the vermis was biopsied. A diagnosis of glioblastoma multiforme was made. He was treated with radiation therapy. Post operatively his major deficits were Ocular Dysmetria, left limb and gait ataxia. In 1970 he immigrated to the US. In 1971 he was referred to Dr. William Sweet, Chief of Neurosurgery at the Massachusetts General Hospital (MGH) with increasing gait ataxia and oscillopsia. Neurological examination: Cranial nerves intact (apart from the eye movements) Motor strength normal Decreased tone in the left extremities Reflexes 2+ throughout with flexor/plantar responses. Coordination: ataxia left extremities Gait ataxia, Romberg negative. Sensory examination normal. Neuro-ophthalmological examination: Visual acuity 20/20 OU Visual fields and pupils normal Fundus exam showed bilateral optic disc drusen Eye movements: •Upbeat nystagmus in primary gaze, increased on up gaze •Square wave jerks •Horizontal gaze evoked nystagmus left > right •Full vertical gaze •Upbeat nystagmus on upgaze •No nystagmus on downgaze •Pursuit, (horizontal and vertical) smooth to a very slow target, markedly saccadic to a fast target •Convergence normal •Marked saccadic hypermetria Right gaze to center overshoot (hypermetria) taking the eyes almost fully to the left Left gaze to center hypermetria taking the eyes almost fully to the right Upgaze to center hypermetria Downgaze to center hypermetria CT scan: In the region of the vermis and the medial portion of the left hemisphere there was an area of high absorption with contrast enhancement involving the cerebellar vermis and medial left cerebellar hemisphere with an apparent associated cystic component consistent with recurrent tumor. Cerebral Arteriogram: A cerebral arteriogram confirmed a highly vascular tumor of the inferior portion of the midline of the cerebellum, bulging into the fourth ventricle. Pathology: The slides from the original biopsy were obtained from Rome and reviewed by Dr E. P. Richardson, Chief of Neuropathology at the MGH. Diagnosis: A high-grade astrocytoma grade 3-4. Surgical procedure: A posterior fossa craniotomy was performed. To access the tumor, the most inferior aspect of the vermis was split to reach the roof of the 4th ventricle. In so doing, a well demarcated tumor nodule was found extending to both sides of the cerebellum, mostly to the left side. It was possible to separate the superior most aspect of the tumor easily from the 4th ventricle. Several small branches of the posterior inferior cerebellar arteries had to be divided to devascularize the tumor which was then gently dissected away from the floor of the 4th ventricle. At the end, the surgeon felt he had as close to a grossly total removal of the tumor as was possible and no visible tumor was left behind. Post operative status: The patient made a good post-operative recovery and was able to walk with an elbow crutch. He continued to be followed by neurosurgery until he was 66 years of age. During that time he had required a shunt revision on two occasions and therapy for an episode of meningitis/cerebritis. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/28
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Supranuclear_Paralysis_of_Vertical_Gaze
Spencer S. Eccles Health Sciences Library University of Utah, 1Co-Authors: Shirley H. Wray, Professor Of Neurology Harvard Medical School, Unit For Neurovisual Disorders, Massachusetts General HospitalAbstract:This case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2007. The patient is a healthy, 36 year old Lieutenant Commander in the Coast Guard who was last seen perfectly well at 2 a.m. on the day of admission. He awoke in the morning around 9 a.m. having over slept - a rare event for him and noticed immediately that his vision was "all askew" due to vertical diplopia. On his way to work he felt tilted to the left and a little off balance tending to veer to the left. His left face was slightly drooped and the left arm and leg were clumsy. When he arrived at the office he was unable to type. The fingers of his left hand were clumsy and failed to hit the keys accurately. He complained of fatigue and attributed this to working almost non-stop for two weeks at his computer to design a software program. Symptomatic Inquiry: Negative for headache, vertigo, speech disturbance, chest pain, shortness of breath or palpitations. Family History: Negative for vascular and neurological disease. On examination: BP 110/60, heart rate 53, normal rhythm. General Neurological Examination: Mild left facial droop No pronator drift and normal motor strength throughout Intact coordination with no Dysmetria Deep tendon reflexes 1+ symmetric Plantar responses flexor Sensory system intact Ocular motility showed: A global supranuclear paralysis of vertical up and downgaze (only 15 degrees up, 5 degrees down from midposition) Vertical saccadic pursuit movements were limited over a similar range of eye movement. Convergence normal Horizontal gaze full Gaze evoked nystagmus to the right Horizontal gaze to the left, mild abduction weakness Ocular Dysmetria: Right gaze to center overshoot (hypermetric) Left gaze to center undershoot (hypometric) Vertical oculocephalic movements intact Bell's reflex intact (eyes deviated up under tightly closed lids). Additional eye signs: A left Ocular tilt reaction (OTR) is a central vestibular disorder involving the vertical vestibulo-Ocular reflex in the roll plane. The key to the diagnosis of an OTR is the combination of a 1.Lateral head tilt to the left in this case. 2.Hypertropia of the undermost eye, left eye, 3.Hypertropia of the contralateral right eye. 4.Fundus photography completes the triad and shows cyclodeviation of the eyes towards the head tilt (excyclotropia of the hypotropic eye; incyclotropia of the hypertropic eye). This patient did not complain of any perceptual tilt of the visual scene or crossed double images. Optokinetic nystagmus (OKN) with rotation of the stripes down, showed convergence retraction nystagmus as he attempted to look up to refixate the stripes. The pupils were abnormal - 5 mm OU with light/near dissociation. Investigations: Initially, there was concern for a diagnosis of endocarditis given the history of recent dental work and night sweats. Blood Studies: Complete blood count and erythrocyte sedimentation rate normal. Blood cultures x 3 negative. Hemocoagulable panel normal. Echocardiogram: A transthoracic and transesophageal echo revealed a patent foramen ovale with left to right shunting by Doppler. Chest x-ray and CT: Showed a right pulmonary embolus and lower lobe infarct. Abdominal/pelvic CT: Normal. Ultrasound and MRV of the lower extremities and pelvis revealed no deep vein thrombosis (DVT). CTA of the head showed: 1.Hyperdensity in the right anterior medial thalamus, consistent with infarction. 2.No hemodynamically significant lesion in the cervical or intracranial arterial circulation 3.Three mm. hypodense nodule in the posterior aspect of the left lobe of the thyroid gland Brain MRI perfusion imaging (7/16/07): 1.A DWI hyperintensity and corresponding ADC hypointensity in the right anterior medial thalamus extending into the right parasagittal midbrain adjacent to the red nucleus. (Figure 1) 2.A very faint FLAIR hyperintensity corresponding to the restricted diffusion image in the right thalamus. Diagnosis: Unilateral embolic infarction in the right anterior medial thalamus extending into the right mesencephalon adjacent to the red nucleus. Treatment: Warfarin sodium (Coumadin) 5 MG. p.o. q. p.m. Enoxaparin (Lovenox) 70 MG SC b.i.d. Discharge Diagnosis: 1.Discreet unilateral embolic infarct of the right paramedian thalamus and upper midbrain in the distribution of the posterior thalamo-subthalamic paramedian artery - the artery of Percheron (1). 2.A clinically silent right lower lobe pulmonary embolus. 3.Patent foramen ovale (PFO) with left to right shunting. Prognosis: The patient was advised that the prognosis for full recovery of his eye movements was excellent. On day 5, the vertical diplopia had resolved with complete resolution of the OTR and skew deviation. Two months later further recovery was noted with: 1.Full vertical gaze with slow vertical saccades most marked on up gaze 2.Looking down from a full upgaze position the eyes lateropulsed to the left or converged. 3.Beats of convergence nystagmus were provoked by a fast upward saccade and OKN with the stripes down. 4.He complained of persistent somnolence and had adopted the habit of setting 3 alarm clocks to wake him each morning. The patient returned 3 months after his acute stroke for closure of the PFO. On examination three weeks later, there was no change in his eye movements. He complained of excessive day time sleepiness. Brain MRI showed a rounded focus of T2 hyperintensity along the medial aspect of the right thalamus at the same location as a lesion with restricted diffusion on the prior brain MRI. (Figures 2A, B and C). See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/29
