Bilateral Ptosis Facial Diplegia

Update Item Information
Identifier 944-1
Title Bilateral Ptosis Facial Diplegia
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 Bilateral Ptosis; Total External Ophthalmoplegia; Facial Diplegia; Areflexia; Acute Inflammatory Demyelinating Neuropathy; Guillian Barre Syndrome - Miller Fisher Syndrome; Facial Weakness
History The patient is a 47 year old attorney who was transferred from an outside hospital to the Massachusetts General Hospital (MGH) for treatmebnt of the Miller Fisher variant of the Guillian Barré syndrome (GBS). On the morning of September 14, 1993, the patient awoke feeling dizzy and he was unsteady walking. He went back to sleep and felt better when he got up and went to work. The next day, he noted horizontal double vision driving to work and he returned home to bed. Later that day, he developed slurred speech and tingling in the right arm and both hands. He went next door to speak to his neighbor, a nurse, and she told him to go to the hospital. He was admitted to a local hospital. Head and Neck MRA: Normal. Lumbar puncture: Cerebrospinal fluid protein 102 mg/ml No white blood cells. Hospital Course: The patient got progressively worse. On day 5, he had the sensation that "someone injected my whole mouth with novocaine" and his speech was profoundly worse. He also reported that his reflexes, which were normal on admission became decreased. On day 10, he was transferred to the MGH. At this time he had mild headache and dizziness and he could no longer hold his eyes open. He recalled that he had had a period of diarrhea one week prior to the onset of these symptoms. On admission he complained of generalized weakness and marked weakness of the face and arms, less in the legs. He was able to chew using the left side of his mouth, but needed to drink with a straw. He had no difficulty swallowing or breathing. Family History: Negative for neurological disease Neurological/ Neuro-ophthalmic examination: Speech dysarthric Cranial Nerves: Complete bilateral ptosis Total external ophthalmoplegia Only a trace of vertical movements up and down Pupils equal, minimally reactive to light and near Facial sensation - Slight decrement of pin sensation bilaterally in all three divisions of the trigeminal nerve. Severe facial diplegia Motor System: He felt generally weak and fatigued, muscle strength was 4+ to 5/5 bilaterally. Deep tendon reflexes 2-4+ in the upper extremities and 1+ in the lower extremities Plantar responses flexor Coordination: Impaired in all four limbs and marked gait ataxia Sensation: Light touch and temperature was decreased distally in the hands and feet Brain CT non-contrast: Normal. Brain MRI: Normal Chest x-ray: Normal EKG: Normal sinus rhythm, normal trace. Diagnosis: Miller Fisher Syndrome (MFS) The constellation of signs: 1. Bilateral ptosis 2. External ophthalmoplegia 3. Facial diplegia 4. Limb and gait ataxia 5. Pupils sluggishly reacting to light 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) Met the criteria for MFS. 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. Electrophysiological studies: Nerve conduction in the lower extremities normal on day 14. Lumbar Puncture: Protein 108 mg/ml No white 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 cultures: Positive for Campylobacter jejuni Serum protein electrophoresis revealed IgG kappa M components in the slow gamma region and there were oligoclonal bands present also. Antibody studies: 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. Treatment: The patient received a total of 6 sessions of plasmaphoresis with replacement with albumin. Ciprofloxacin 500 mg. p.o., b.i.d. Hospital Course: Initially, the patient was too weak to get out of bed and he became areflexic. He started to improve while receiving plasmaphoresis and physical therapy to the point that at five weeks post onset of his illness he regained a few degrees of eye movement in all directions, the ptosis resolved and he was able to open his eyes. He also gained more control of his mouth and lips resulting in improvement in his speech but he was unable to smile or whistle. Follow-Up: The patient was seen in the clinic at five weeks, twelve weeks and four months after the onset of his illness. By four months, the ptosis and ophthalmoplegia had resolved completely and he had minimal facial weakness and speech was 90% back to normal. He had 5/5 muscle strength and no ataxia.
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 inflammatory demyelinating neuropathy. 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. 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.
Disease/Diagnosis Miller Fisher Syndrome; Acute inflammatory demyelinating neuropathy
Clinical This patient with a severe attack of MFS was followed over a period of four months. I had the opportunity to film him on four occasions. In the first clip, made on day 15 he had: Complete ptosis Total external ophthalmoplegia Inability to close his eyes tightly Unable to raise his eyebrows Severe facial diplegia with inability to show his teeth or smile Dyarthric speech due to inability to articulate his words The second clip was made at five weeks. At this time: Ptosis had started to improve Able to open and close his eyes Not able to blink -- definite paucity of blinking Facial diplegia still pronounced and unable to show his teeth External ophthalmoplegia beginning to improve Partial recovery of horizontal gaze to right and left and vertically Gait ataxia much improved and no limb ataxia The third clip was made at twelve weeks. At this time he reported: General strength recovering Full use of his hands and arms Speech was a good deal clearer. Ptosis had recovered and he was aware of diplopia Able to close his eyes fairly tightly Raise his eyebrows up and Grip his lips together but could not whistle. The fourth clip was made at four months. At this time, striking improvement and a much happier man. Speech clearer but still not precise. External ophthalmoplegia has completely recovered with full horizontal and vertical eye movements Lip movements improved Able to grip his lips together Eye closure now tight and able to open and close his eyes normally Raise his eyebrows up and frown Lower face weakness improved, able to show his teeth and smile No gait ataxia Reflexes 1+ throughout 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".
Presenting Symptom Double Vision
Ocular Movements Bilateral Ptosis; Total External Ophthalmoplegia; Facial Diplegia
Neuroimaging No imaging studies are available in this patient. The MRI findings in another patient with the 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.
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). Approximately 3 to 5% of patients do not survive an attack of GBS.78.
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.
Supplementary Materials Miller Fisher Syndrome: https://collections.lib.utah.edu/details?id=2174209
Date 1993
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Language eng
Format video/mp4
Type Image/MovingImage
Source 3/4" Umatic master videotape
Relation is Part of 925-2, 944-5
Collection Neuro-Ophthalmology Virtual Education Library - Shirley H. Wray Neuro-Ophthalmology 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/s6kq0zpk
Setname ehsl_novel_shw
ID 188510
Reference URL https://collections.lib.utah.edu/ark:/87278/s6kq0zpk