Bilateral Ptosis Facial Diplegia

Update item information
Identifier 925-2
Title Bilateral Ptosis Facial Diplegia
Ocular Movements Bilateral Ptosis: Total External Ophthalmoplegia: Normal Pupils
Creator Shirley H. Wray, M.D., Ph.D., FRCP, Professor of Neurology Harvard Medical School, Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Contributor Primary Shirley H. Wray, MD, PhD, FRCP, Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Subject Bilateral Ptosis; Total External Ophthalmoplegia; Normal Pupils; Facial Diplegia; Areflexia; Acute Inflammatory Demyelinating Neuropathy; Guillian Barre Syndrome - Miller Fisher Syndrome
Supplementary Materials PowerPoint Presentation: Miller Fisher Syndrome: Sarah I. Sheikh, BM. B.Ch., MRCP Massachusetts General Hospital
Presenting Symptom Double vision
History The patient is a 74 year old woman who one month prior to admission suffered from a non-productive cough, right ear pain, and pharyngitis treated with amoxicillin. On the day prior to admission she awoke with blurred vision and horizontal and vertical diplopia that persisted all day. The next morning she was worse with ptosis of the right eyelid and difficulty "navigating" around her home. She consulted her ophthalmologist and was referred to the Massachusetts Eye and Ear Infirmary and then referred to the Massachusetts General Hospital Emergency Room. Neuro-ophthalmological examination: Bilateral ptosis with palpebral fissures of 1.5 mm OU External ophthalmoplegia: Upgaze severely limited to 35° OS and 15° OD Downgaze limited 45° OS and 15° OD Horizontal eye movements, bilateral weakness of adduction with no nystagmus of the abducting eye Absent deviation of the eyes up under closed lids (Bell's phenomenon) Anisocoria, left pupil slightly larger than the right, both reacted briskly to light and near. Neurological examination: Facial diplegia Motor and sensory system normal Reflexes 2+ throughout and symmetrical Flexor plantar responses Coordination: Mild gait ataxia, no limb ataxia Investigations: The most important investigations in suspected cases of the Guillian Barré syndrome (GBS) or the variant, the Miller Fisher syndrome (MFS) are: 1. Electrodiagnostic studies and 2. Examination of the cerebrospinal fluid (CSF) The most frequent early electrodiagnostic findings in GBS and MFS are: 1. A reduction in the amplitude of muscle action potentials 2. Slow nerve conduction velocity 3. Conduction block in motor nerves singly or in combination 4. Prolonged distal latencies (reflecting distal conduction block) 5. Prolonged or absent F-responses (indicating involvement of proximal parts of nerves and roots) and reflecting focal demyelination. 6. Delayed or absent H-reflex (which really just confirms the loss of ankle jerks). A limited electrodiagnostic examination may be normal early in the illness as in this case. A more thorough study, which includes measurement of late responses, almost invariably shows disordered conduction in an affected limb within days of the first symptom. Electrodiagnostic studies: In this patient electrodiagnostic studies were done on day 14 when the deep tendon reflexes were present and showed no abnormality. Lumbar Puncture: Cerebrospinal fluid protein 54 mg/dl No white blood cells Usually, the CSF protein is normal in the first few days of the illness. Then the protein level begins to rise reaching a peak in 4 to 6 weeks and persisting elevated for several weeks. In Dr. Ropper's experience patients with MFS have a higher incidence of normal or only slightly elevated CSF protein during the course of their illness. Stool Culutres: No stool cultures were obtained. Diagnosis: Miller Fisher Syndrome (MFS) Hospital Course: Over the next several days, the patient's signs progressed to complete bilateral ptosis and significant weakness of abduction and adduction of both eyes. Vertical ophthalmoplegia became complete. At this time, the patient became areflexic. Treatment: Intravenous immunoglobulin (0.4 g/kg per day for five consecutive days) The patient was hospitalized for 21 days. At the time of discharge there was a 50% improvement in bilateral ptosis, and in abduction of both eyes. Vertical gaze remained paretic. She was discharged to the care of her sister and returned to the neuromedical clinic four weeks later. She had considerable improvement in her ptosis and ophthalmoplegia. Two months later she had made a full recovery.
Clinical This patient with the Miller Fisher Syndrome (MFS) a variant of the Gullian Barre Syndrome (GBS) had the following signs: On hospital day 5 she had: Mild bilateral asymmetrical ptosis Overaction of the frontalis muscle Gaze right, adduction weakness of the left eye No nystagmus of the abducting right eye Gaze left, adduction weakness of the right eye No nystagmus of the abducting left eye Vertical gaze absent Absent Bell's phenomenon Absent convergence and Recovering facial diplegia with Mild bilateral facial weakness Weak whistle In 1956 Miller Fisher published a paper in the New England Journal of Medicine describing an unusual acute idiopathic polyneuritis characterized by: 1. Total external ophthalmoplegia 2. Severe ataxia and 3. Loss of the deep tendon reflexes The nature of the illness was not recognized until he saw the third case, when, in association with a mild peripheral neuropathy, the cerebrospinal fluid showed an albuminocytologic dissociation with a total protein of 348 mg/100 ml. and no cells. The syndrome Miller Fisher described proved to be a variant of acute idiopathic polyneuritis (GBS) in which limb involvement was minimal or absent. In two of Miller Fisher's cases, (case 1 and 2) external ophthalmoplegia was complete and the eyes fixed in primary gaze. Case 3 had bilateral sixth nerve paralysis and slight rotary nystagmus on attempted lateral gaze. Bilateral ptosis was added to the picture two days later. GBS is now viewed as a group of distinct disorders which include the following variants, tabulated by Ropper and Brown (Table 46-3 (18)). Regional Fisher syndrome of ophthalmoplegia, ataxia and areflexia Cervico-brachial-pharyngeal, often with ptosis Oculopharyngeal weakness Predominant paraparesis Bilateral facial or abducens weakness with distal paresthesias Ophthalmoplegia with GQ1b autoantibodies Functional Generalized ataxia without dysarthria or nystagmus Pure sensory Pure motor Pandysautonomia Axonal The degree of ophthalmoparesis is variable but certain patterns suggest involvement of either the peripheral or central nervous system. The ophthalmoplegia may resemble: Horizontal or vertical gaze palsy Internuclear ophthalmoplegia, and Ptosis is often absent even in the presence of significant ophthalmoparesis. Bell's phenomenon is often preserved even when vertical eye movements are absent. Signs pointing to cerebellar dysfunction are: Rebound nystagmus Impairment of smooth pursuit Suppression of the vestibular ocular reflex Dr. Fisher was himself impressed by the presence of ataxia unaccompanied by sensory loss, and "reluctantly interpreted" the clinical signs as "manifestations of an unusual and unique disturbance of peripheral neurons".
Neuroimaging No imaging studies are available in this patient. The MRI findings in another patient with MFS have been reported. The patient was a 25 year old woman with complete external ophthalmoplegia, ptosis, limb ataxia and areflexia. Brain MRI: T1-weighted images with Gd-DTPA on day 15 of her illness, demonstrated enhancement of the posterior nerve roots of the cauda equina. MRI on day 32 revealed swelling and enhancement of the bilateral ocular motor nerves, as well as the facial nerves and the abducen nerves. The patient received high-dose intravenous immunoglobulin therapy and had marked improvement in her ophthalmoplegia. Repeat MRI with gadolinium, after recovery, showed no enhancement of the cauda equina nor of the cranial nerves. In this patient IgG anti-GQ1b and GD1b antibodies were detected.
Pathology In 1993, Chiba et al reported the presence of serum IgG antibody against ganglioside GQ1b in patients in the acute phase of the Miller Fisher syndrome and pointed out that this immunologic feature was common to both MFS and GBS. To check for Anti-GQ1b antibody, I sent the serum of this patient and the serum from a second case of MFS, a young man presenting with bilateral sixth nerve palsy, (ID944-5) to Professor Newsom-Davis in Oxford to study. Both these patients were found to have the Anti-GQ1b IgG antibody. Both GBS and the MFS are cell mediated immunological diseases directed at peripheral nerve resulting in acute idiopathic polyneuritis. Autoantibodies: A number of autoantibodies directed at components of nerve ganglioside are detected inconsistently in patients with GBS. Anti-GQ1b IgG is the most important and is the autoantibody found in almost all patients with ophthalmoplegia. Antibodies against the ganglioside GQ1b have also been detected in patients with Bickerstaff's brainstem encephalitis. Bickerstaff's encephalitis is characterized by ophthalmoplegia and ataxia but is also accompanied by pyramidal and sensory tract findings and cerebrospinal fluid pleocytosis. GM1 autoantibody may be found in approximately one-third of patients with GBS early in their course, corresponding in most instances to a predominantly motor presentation and to axonal damage. The highest titres of anti-GM1 antibody are usually associated with cases that follow Campylobacter infections. Autoantibodies directed against GD1a or GT1b have been associated in some cases with the pharyngeal-brachial-cervical variant. Pathology: Pathological studies in cases of GBS have failed to demonstrate any changes within the neuroaxis, and there is thus no morbid anatomic basis for attributing the clinical picture to a disturbance within the brainstem. Virtually all cases have shown perivascular (mainly perivenous) lymphocytic infiltrates scattered throughout the cranial nerves, ventral and dorsal nerve roots and dorsal root ganglia and along the entire length of the peripheral nerves. Swelling of nerve roots at the site of their dural exit has been emphasized by some authors and theorized to cause root damage. In patient's whose electrophysiologic tests display severe axonal damage early in the illness, the pathologic findings corroborate the predominately axonal nature of the disease with secondary myelin damage and little inflammatory response.
Etiology Campylobacter jejuni may be the responsible trigger in GBS and MFS since Anti-GQ1b antibodies bind to surface epitopes on this organism, and its lipopolysaccharide fraction may molecularly mimic the ganglioside.
Disease/Diagnosis Miller Fisher Syndrome; Acute inflammatory demyelinating neuropathy
Treatment Specific treatment of the presumed immune disorder that underlies GBS and the Miller Fisher Syndrome include plasma exchange and intravenous immunoglobulin IVIG (0.4 g/kg per day for five consecutive days). IVIG stops Anti-GQ1b antibodies from binding to GQ1b ganglioside receptors and thereby prevents the electrophysiological effects. Approximately 3 to 5% of patients do not survive an attack of GBS.78.
References 1. Al-Din ASN, Anderson M, Bickerstaff ER, Harvey I. Brainstem encephalitis and the syndrome of Miller Fisher. Brain 1982;105:481-495. 2. Ang CW, Laman JD, Willison HA et al. Structure of Campylobacter jejuni lipopolysaccharides determines antiganglioside specificity and clinical features of Guillian-Barre and Miller Fisher patients. Infect Immun 2002;70:1202-1208. 3. Jean Baptiste Octave Landry de Thézillat. Paralysies. Gazette hebdomadaire de médecine et de chirurgie, 1859, 6: 472-474. 4. Berlit P, Rakicky J. The Miller Fisher Syndrome. Review of the Literature. J Clin Neuro-ophthalmol 1992;12(1):57-63. 5. Caccavale A, Mignemi L. Acute onset of a bilateral areflexical mydriasis in Miller Fisher syndrome: a rare neuro-ophthalmologic disease. J Neuroophthalmol 2000;20(1):61-62. 6. Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: Clinical and immunohistochemical studies. Neurology 1993;43(10):1911-1917. 7. Fisher CM. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med. 1956;225(2):57-65. 8. Guillain G, Barré JA, Strohl A. Le réflexe médico-plantaire: Étude de ses caracteres graphiques et de son temps perdu. Bulletins et mémoires de la Société desMédecins des Hôpitaux de Paris 1916;40:1459-1462. 9. Guillain G, Barré JA, Strohl A. Sur un syndrome de radiculonévrite avec hyperalbuminose du liquide céphalo-rachidien sans réaction cellulaire. Remarques sur les caractères cliniques et graphiques des réflexes tendineux. Bulletins et mémoires de la Société desMédecins des Hôpitaux de Paris 1916;40:1462-1470. 10. Hattori M, Takada K, Yamada K, Kamimoto K, Mitake S. A case of Miller Fisher syndrome with gadolinium-enhancing lesions in the cranial nerves and the cauda equine on magnetic resonance imaging. Rinsho Shinkeigaku 1999; 39(10):1054-1058. 11. Jacobs BC, O'Hanlon GM. Bullens RW, Veitch J, Plomp JJ, Willison HJ. Immunoglobulins inhibit pathophysiological effects of anti-GQ1b-positive sera at motor nerve terminals through inhibition of antibody binding. Brain 2003;126:2220-2234. 12. Keane JR. Bilateral seventh nerve palsy. Analysis of 43 cases and review of the literature. Neurology 1994;44:1198. 13. Leigh RJ, Zee DS. Diagnosis of Peripheral Ocular Motor Palsies and Strabismus. In: The Neurology of Eye Movements 4th Edition. Oxford University Press, New York 2006, Chp 9:385-474. 14. Meienberg O, Ryffel E. Supranuclear eye movement disorders in Fisher's syndrome of ophthalmoplegia, ataxia, and areflexia. Report of a case and literature review. Arch Neurol. 1983 Jul;40(7):402-5. 15. Mori M, Kuwabara S, Fukutake T, Yuki N, Hattori T. Clinical features and prognosis of Miller Fisher syndrome. Neurology 2001;56(8):1104-1106. 16. Newsom-Davis J.. Myasthenia gravis and the Miller-Fisher variant of GBS. Curr-Opin-Neurol. 1997;10(1):18-2. 17. Ohtsuka K, Nakamura Y, Hashimoto M, Tagawa Y, Takahashi M, Saito K, Nobuhiro Y. Fisher Syndrome Associated with IgG Anti-GQ1b Antibody Following Infection by a Specific Serotype of Campylobacter jejuni. Ophthalmology 1998;105(7)1281-1285. 18. Ropper, AH, Brown RH. Disease of The Peripheral Nerves Chp 46:1110-1177. In: Adams and Victor's Principles of Neurology, Eighth Edition, McGraw Hill, 2005. 19. Sato K, Yoshikawa H. Bilateral abducens nerve paresis associated with anti-GQ1b IgG antibody. Am J Ophthalmol 2001;131(6):816-818. 20. Shimamura H, Miura H, Iwaki Y, Kubodera T, Matsuoka T, Yuki N, Koga M. Clinical, electrophysiological, and serological overlap between Miller Fisher syndrome and acute sensory ataxic neuropathy. Acta Neurol Scand 2002;105:411-413. 21. Shuaib A, Becker WJ. Variants of Guillain-Barre syndrome: Miller Fisher syndrome, facial diplegia and multiple cranial nerve palsies. Can J Neurol Sci 1987;14(4):611-616. 22. Susuki K, Atsumi M, Koga M, Hirata K, Yuki N. Acute facial diplegia and hyperreflexia: A Guillain-Barre syndrome variant. Neurology 2004;62 (5):825-827. 23. Swick HM. Pseudointernuclear ophthalmoplegia in acute idiopathic polyneuritis (Fisher's syndrome). Am J Ophthalmol. 1974 May;77(5):725-8. 24. Takahashi M, Koga M, Yokoyama K, Yuki N. Epidemiology of Campylobacter jejuni isolated from patients with Guillian-Barre and Fisher syndrome in Japan. J Clin Microbiol 2005;43:335-339. 25. van Doorn PA, Ruts, L and Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol;2008;7:939-950. 26. Willison HJ and Plomp JJ. Anti-ganglioside antibodies and the presynaptic motor nerve terminal. Annals of the NY Acad Sci 2008;1132:114-123. 27. Yuki N, Odaka M, Hirata K. Acute ophthalmoparesis (without ataxia) associated with anti-GQ1b IgG antibody: clinical features. Ophthalmology 2001;108(1):196-200. 28. Yuki N. Sato S, Tsuji S, Hozumi I, Miyatake T. An immunological abnormality common to Bickerstaff's brain stem encephalitis and Fisher's syndrome. J Neurol Sci 1993;131:108-110.
Relation is Part of 944-1, 944-5
Contributor Secondary Ray Balhorn, Video Compressionist; Steve Smith, Videographer
Publisher Spencer S. Eccles Health Sciences Library, University of Utah
Date 1990
Type Image/MovingImage
Format video/mp4
Source 3/4" Umatic master videotape
Rights Management Copyright 2002. For further information regarding the rights to this collection, please visit:
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E, SLC, UT 84112-5890
Collection Neuro-ophthalmology Virtual Education Library: NOVEL
Language eng
ARK ark:/87278/s6bw0d5s
Setname ehsl_novel_shw
Date Created 2005-08-22
Date Modified 2017-11-27
ID 188566
Reference URL
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