| Identifier |
165-10 |
| Title |
Titubation Opsoclonus |
| Creator |
Shirley H. Wray, MD, PhD, FRCP |
| Affiliation |
(SHW) Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital, Boston, Massachusetts |
| Subject |
Titubation; Opsoclonus; Oscillopsia; Saccadic Oscillations; Paraneoplastic Cerebellar Syndrome; Adenocarcinoma of the Breast; Anti-Ri Antibody; Paraneoplastic Opsoclonus; Divergence |
| History |
This 52 year old woman presented with unsteady gait. She was admitted to an outside hospital where a diagnosis was made. 1. Paraneoplastic opsoclonus 2. Paraneoplastic cerebellar syndrome with bilateral limb and gait ataxia and titubation 3. Adenocarcinoma of the breast She was transferred to the Massachusetts General Hospital (MGH) for possible plasmaphoresis therapy. View alongside this case three additional cases of paraneoplastic opsoclonus in this collection. ID931-1 The index case of the Anti-Ri antibody with paraneoplastic opsoclonus and intraductal adenocarcinoma of the breast ID936-7 Opsoclonus/ocular flutter, a remote manifestation of cancer of the lung ID936-8 Opsoclonus and ataxia in a young child with neuroblastoma Other reported causes of opsoclonus in adults include: Thalamic hemorrhage Multiple sclerosis Hyperosmolar coma and Toxic side effects from drugs such as thalium and toluene Most patients however with opsoclonus fit into four clinical groups: Parainfectious brainstem encephalitis (view ID942-3) Paraneoplastic syndromes Metabolic-toxic states Idiopathic Paraneoplastic Markers: This patient was seen prior to the discovery in 1985 of the Anti-Ri antibody by Dr. Posner in a patient of mine who had paraneoplastic opsoclonus and intraductal adenocarcinoma of the breast. The Anti-Ri antibody has become a marker for patients with breast and gynecological cancer. Ri Autoantibody Test 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) A second antibody, the Anti-Yo antibody is a marker for paraneoplastic cerebellar degeneration in which the Purkinje cells are destroyed and ataxia progresses. Yo Autoantibody Test Antibodies to the Yo antigen are the most common paraneoplastic antibodies to Purkinje cells. A negative result for the Yo autoantibody test proved that the cause of the disease was not due to this paraneoplastic antibody but does not rule out paraneoplastic cerebellar degeneration as the cause of the symptoms (1,2). 1. Hammack J. et al. Neurology 1992;42:1938-1943. 2. Clouston PD et al. Neurology 1992;42:1944-1950. |
| Pathology |
Paraneoplastic opsoclonus/ocular flutter is thought to be humorally mediated, and antibodies to diverse auto-antigens have been reported, but most patients are seronegative. The antineural antibodies associated with opsoclonus include Anti-Ri, Anti-Hu, Anti-Yo, Anti-Mal, and Anti-amphyphisin antibodies. Opsoclonus (OC) is characterized by omnidirectional saccadic oscillations. It is not known however whether OC is a cerebellar or brainstem disorder. Cerebellar theory: Wong et al have suggested, on theoretical grounds, that the deep cerebellar nuclei should be activated in patients with opsoclonus. (16) Helmchen et al 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. (8) 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 vermal nor brainstem activation but showed, for the first time, bilateral functional activation of the deep cerebellar nuclei. This result supports Wong et al's recent hypothesis that OC results from a disinhibition of the fastigial ocular motor region (FOR). The 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 the FOR, the authors concluded that the absence of vermal activation during OC may reflect a cause of OC. Brainstem theory: 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 suggests that it may be possible that membrane-stabilizing drugs may find a therapeutic role for flutter and opsoclonus in the future. (Personal communication, 2007) (For further discussion (12)). |
| Disease/Diagnosis |
Paraneoplastic opsoclonus; Paraneoplastic cerebellar degeneration; Adenocarcinoma of the breast View Paraneoplastic Opsoclonus to see figures, tables and pathology |
| Clinical |
This patient with adenocarcinoma of the breast had: • Sustained opsoclonus • Multidirectional conjugate saccades of large amplitude without an intersaccadic interval • Opsoclonus under closed eyelids and in sleep She also had cerebellar signs: • Titubation of the head • Bilateral limb ataxia • Gait ataxia She died several months later. |
| Presenting Symptom |
Unsteady gait |
| Ocular Movements |
Titubation; Opsoclonus |
| Neuroimaging |
No imaging studies are available in this patient. |
| Treatment |
The approach to treatment in paraneoplastic opsoclonus syndromes is: 1. Appropriate therapy for the cancer • Surgery • Chemotherapy and/or Radiation 2. Immune modulation • Plasmapheresis • Immunoadsorption Therapy • Intravenous immunoglobulin • Steroids 3. Symptomatic treatment for vertigo etc. |
| Etiology |
Autoimmune: occult adenocarcinoma of the breast |
| Date |
1980 |
| References |
1. 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 2. Averbuch-Heller L, Remler B. Opsoclonus. Semin Neurol 1996;16:21-26. http://www.ncbi.nlm.nih.gov/pubmed/8879053 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. Bataller L, Dalmau J. Neuro-ophthalmology and paraneoplastic syndromes. Curr Opin Neurol 2004;17:3-8. http://www.ncbi.nlm.nih.gov/pubmed/15090871 5. 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 6. 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. Ellenberger C, Jr. Campa JF, Netsky MG. Opsoclonus and parenchymatous degeneration of the cerebellum. The cerebellar origin of an abnormal eye movement. Neurology 1968;18:1041-1046. http://www.ncbi.nlm.nih.gov/pubmed/5752588 8. Francis DA, Heron JR. Ocular flutter in suspected multiples sclerosis: a presenting paroxysmal manifestation. Postgrad Med J 1985;61:333-334. http://www.ncbi.nlm.nih.gov/pubmed/4022865 9. Hain RC, ZeeDS, Mordes M. Blink-induced saccadic oscillations. Ann Neurol 1986;19:299-301. http://www.ncbi.nlm.nih.gov/pubmed/3963775 10. 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 11. Koukoulis A, Cimas I, Gomara S. Paraneoplastic opsoclonus associated with papillary renal cell carcinoma. J Neurol Neurosurg Psychiatry 1998;64:137-138. http://www.ncbi.nlm.nih.gov/pubmed/9436748 12. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusion. Part 2: Chp 10;521-534. In: The Neurology of Eye Movements. 4th Ed. Oxford University Press, New York 2006. 13. Luque AF. Furneaux HM, Ferziger R, Rosenblum MK, Wray SH, Schold SC Jr, Glantz MJ, Jaeckle KA, Biran H, Lesser MK, Paulsen WA, River ME, Posner JH. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991;29:241-251. http://www.ncbi.nlm.nih.gov/pubmed/2042940 14. Schon F, Hodgson TL, Mort D, Kennard C. Ocular flutter associated with a localized lesion in the paramedian pontine reticular formation. Ann Neurol 2001;50:413-416. http://www.ncbi.nlm.nih.gov/pubmed/11558800 15. Shams'ili S, Grefkens J, de Leeuw, B, van den Bent M, Hooijkaas H, van der Holt, Bronno, Vecht C, and Smitt, PS. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain 2003;126:1409-1418. http://www.ncbi.nlm.nih.gov/pubmed/12764061 16. 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/11535236 |
| Language |
eng |
| Format |
video/mp4 |
| Type |
Image/MovingImage |
| Source |
16 mm. Film |
| Relation is Part of |
166-12, 931-1, 936-7, 936-8 |
| Collection |
Neuro-Ophthalmology Virtual Education Library: Shirley H. Wray Collection: https://novel.utah.edu/Wray/ |
| Publisher |
North American Neuro-Ophthalmology Society |
| Holding Institution |
Spencer S. Eccles Health Sciences Library, University of Utah |
| Rights Management |
Copyright 2002. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright |
| ARK |
ark:/87278/s6254fth |
| Setname |
ehsl_novel_shw |
| ID |
188638 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6254fth |
