Journal of Neuro-Ophthalmology, June 1993, Volume 13, Issue 2

Miller Fisher syndrome mimicking stroke in immunosuppressed patient with rheumatoid arthritis responding to plasma exchange.

A patient with rheumatoid arthritis on immunosuppressive therapy was admitted to hospital with the sudden onset of diplopia and ataxia. Because of the history, a stroke was thought most likely. However, as he progressed a diagnosis of the Miller Fisher syndrome was established. He responded to plasma exchange. This presentation is highly unusual and has not previously been described. In addition, the possibility of immune dysregulation setting the stage for the development of this syndrome is discussed. The role of plasma exchange for this condition is also reviewed.

© 1993 Raven Press, Ltd, .~w York Miller Fisher Syndrome Mimicking Stroke in Immunosuppressed Patient with Rheumatoid Arthritis Responding to Plasma Exchange Lawrence M. Cher, M.B.B.S., B.Sc (Med) and John M. Merory, M.B.B.S., F.R.A.C.P. A patient with rheumatoid arthritis on immunosuppres­sive therapy was admitted to hospital with the sudden onset of diplopia and ataxia, Because of the history, a stroke was thought most likely, However, as he pro­gressed a diagnosis of the Miller Fisher syndrome was established. He responded to plasma exchange. This presentation is highly unusual and has not previously been described. In addition, the possibility of immune dysregulation setting the stage for the development of this syndrome is discussed. The role of plasma exchange for this condition is also reviewed. Key Words: Miller Fisher syndrome-Rheumatoid ar­thritis- Stroke-Immunodysregulation-Plasma ex­change. From the Department of Neurology, Heidelberg Repatriation Hospital, Heidelberg West, Melbourne, VIC Australia, Address correspondence and reprint requests to Dr. John M. Merory, Department of Neurology, Heidelberg Repatriation Hospital, Heidelberg West, Melbourne VIC, Australia. 138 The Miller Fisher Syndrome (1) is well known and is usually regarded as a variant of the acute inflammatory demyelinating polyradiculoneurop­athies or Guillain-Barre syndrome (2-4), although there have been dissenting opinions (5,6). We are unaware of any reports of this syndrome begin­ning paroxysmally, mimicking a vascular event. The occurrence of Miller Fisher syndrome in a pa­tient with rheumatoid arthritis on immunosup­pressive therapy may have been a random event. Consideration is given to a possible relationship between these two disorders. CASE REPORT The patient was a 66-year-old male with a 5-year history of rheumatoid arthritis. He previously had symmetrical polyarthritis, rheumatoid nodules, and interstitial lung disease. His disease was stable and controlled with low-dose prednisolone (5 mg), methotrexate (10 mg weekly), and hydroxychloro­quine (400 mg bid). At 3 weeks prior to admission he developed a flu-like illness with pharyngitis, myalgias, and lethargy, and 5 days prior to admission he sud­denly developed horizontal diplopia and frontal headache while driving. On leaving the car his gait was unsteady. This continued for the following 4 days and was accompanied by vertigo, tinnitus, and subjective hearing impairment. He was admit­ted to hospital. Examination demonstrated dilated but equal pu­pils, which reacted sluggishly to light. Horizontal gaze-evoked nystagmus was more prominent in the abducting eye in either direction (dissociated nystagmus). Adducting saccades were normal and therefore not typical of internuclear ophthalmople- MILLER FISHER SYNDROME MIMICKING STROKE 139 gia. No other cranial nerve abnormality was de­tected. Tone and power were normal, but a mod­erately severe truncal ataxia was demonstrated. Deep tendon reflexes were absent. Sensory testing revealed loss of vibration in the lower limbs and trunk to the lower thorax. Cerebral computed to­mography (CT) scans with fine cuts through the posterior fossa was normal as was a Tensilon test. Erythrocyte sedimentation rate (ESR) was 25 mmlh. Over the next 2 days, he progressively devel­oped external ophthalmoplegia, moderate bilateral ptosis, and facial diplegia, and very diminished pupillary light reflexes. Horizontal eye movements were restricted to 20 degrees rightward and 30 de­grees leftward. Upgaze was limited to 15 degrees and downgaze to 10 degrees. Nerve conduction studies were normal except for prolonged F waves suggesting proximal nerve involvement. Cerebro­spinal fluid (CSF) analysis showed normal glucose, and protein of 0.46 giL with no cells. Viral cultures of CSF were normal. A diagnosis of Miller Fisher syndrome was made. Because his condition was progressive he was treated with plasma exchange (3 Llday for 5 days). This was complicated by mild hypotension. Whereas previously his clinical state had wors­ened, with commencement of treatment no further deterioration occurred. By day 4 of plasma ex­change, he started to improve and this continued such that his gait became normal, and ptosis re­solved. The diplopia persisted as did the areflexia. Over the next 5 weeks, his tendon reflexes and pupillary light reflexes returned and his ophthal­moplegia resolved. DISCUSSION We are unaware of any reported cases of Miller Fisher syndrome that have begun paroxysmally as with our patient. The importance of the history in establishing the diagnosis in neurological prob­lems is always stressed. However, in this case the clear history of sudden onset caused diagnostic confusion and delay in definitive therapy. The sudden onset of diplopia and unsteady gait and vertigo, associated with nystagmus and truncal ataxia is usually due to a vascular event. The "dis­sociation" between history and signs was perplex­ing initially until the development of external and internal ophthalmoplegia completed the clinical picture of areflexia, ataxia, and absent vibration sense. Although acute inflammatory demyelinat­ing polyradiculoneuropathies can have a rapidly progressive course, patients do not describe such abrupt commencement of symptoms. One possi­ble mechanism to explain the sudden onset of symptoms is the sudden decompensation of pro­gressive oculomotor weakness. However, this does not explain the simultaneous onset of ataxia. The association with rheumatoid arthritis may be more than fortuitous. Neuropathy in patients with rheumatoid arthritis has been well docu­mented (7) but the etiology has been unclear. The literature contains anecdotal reports of the associ­ation between rheumatoid arthritis and acute in­flammatory demyelinating polyradiculoneuropa­thy and chronic inflammatory demyelinating poly­neuropathy. In a review of 66 consecutive patients with acute and chronic inflammatory demyelinat­ing polyneuropathy seen at one hospital, 15% had associated autoimmune disorders, including one with rheumatoid arthritis and acute inflammatory demyelinating polyneuropathy (8). The occurrence of Miller Fisher syndrome in a patient with rheu­matoid arthritis has been documented (9). This was attributed to concomitant gold therapy, as gold has been associated with acute inflammatory demyelinating pOlyneuropathy (10). However, rheumatoid arthritis may have been the underly­ing factor. It has been suggested (11-13) that immunosup­pression may play a role in the pathogenesis of acute inflammatory demyelinating polyneuropa­thy. Interestingly, the patient described by Mon­teiro and colleagues (12) developed Miller Fisher syndrome following 5 weeks of prednisone ther­apy for angioimmunoblastic lymphadenopathy, a condition with both autoimmune and immunode­ficient features. They postulated that the immuno­logic deficiency may be crucial to the development of acute inflammatory demyelinating polyneurop­athy by impairing T-suppressor cell function lead­ing to immune dysregulation. The three patients described by Lisak and coworkers (11) with inflam­matory demyelinating polyneuropathy and Hodg­kin's disease all showed evidence of impaired cell­mediated immunity (CMI) (11). They refer to the occurrence of acute inflammatory demyelinating polyneuropathy in patients with variable degrees of immunosuppression, such as systemic lupus er­ythematosis, pregnancy, and after cytomegalovi­rus (CMV) or Epstein-Barr virus (EBV) infections. They suggest that selective depression of CMI from whatever cause could perturb those aspects of the immune system which prevent self-directed immune events. The occurrence of acute inflam­matory demyelinating in a renal transplant patient (13) on prednisone and azathioprine furnishes fur­ther evidence that immunosuppression does not I Gin Neuro-ophthalmol, Vol. 13, No.2, 1993 L. M. CHER AND J. M. MERORY ~ . '_Ii"velopment of an autoimmune dis­ease '.>';~ lcrl:'st, long-term low-dose methotrexate h",; :-~'cn ,;hown ttl increase T-4 (helper) cells and ,,:'ease T-8 (suppressor) cells (14). Gold has im­r" unomodulatory effects as well, most likely via the monocyte-macrophage system (15). Therefore, perhaps it is the immunosuppressive regime (whether it be gold or methotrexate etc.) rather than the underlying disease which is related to the occurrence of Miller Fisher syndrome in our pa­tient. The role of plasma exchange in Miller Fisher syndrome has not been systematically assessed. To our knowledge only one individual case report has been published (16), and a passing reference is made in another (17). This therapy has proven to be of benefit in acute inflammatory demyelinating polyneuropathy (18). In a review of cases of acute inflammatory demyelinating polyneuropathy at Royal Prince Alfred Hospital (Sydney, Australia) Pollard mentioned six patients with Miller Fisher syndrome, five of whom were treated with plasma exchange because of severe ataxia. All responded clinically (unpublished data). Although the length of time to recovery in Miller Fisher syndrome is variable, in most case reports the average time course to recovery was approxi­mately 3 to 4 months. Reviewing 10 cases from various reports in which it was possible to estimate the time to recovery from symptoms and signs, the average length of duration was 6.7 months with a mean of 5 months. Sauron and coworkers (19) re­ported 10 patients who were asymptomatic within 1 to 3 months. Although Miller Fisher syndrome is usually thought to be a benign condition cases have been reported who progressed to intubation and ventilation (20). Our patient was clearly pro­gressing and plasma exchange led to stabilisation initially and then improvement to normal over 5 weeks. While too much weight should not be given to single case reports of plasma exchange in acute inflammatory demyelinating pOlyneuropa­thy, it is unlikely that a large enough series of pa­tients with Miller Fisher syndrome could be gath­ered to perform a controlled trial. Most neurolo­gists would treat Miller Fisher syndrome with plasma exchange. As this modality of therapy is most effective when commenced early, the delay in diagnosis of patients such as ours could be im­portant. REFERENCES 1- Fisher M. An Unusual variant of acute idiopathic polyneu­ritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engll Med 1956;255:57--65. 2. Ropper AH. The CNS in Guillain-Barre syndrome. 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