Electrophysiologic study of Fisher syndrome

Electrophysiologic studies were performed on a 6-year-old girl with Fisher syndrome. We recorded several evoked potentials in this patient: visual evoked potentials, auditory brainstem responses, auditory evoked potentials, short-latency somatosensory evoked potentials, blink reflex elicited by photic stimuli (photo-evoked eyelid microvibration), blink reflex elicited by auditory stimuli (auditory evoked eyelid microvibration), and motor nerve conduction velocity. In our study, photo-evoked eyelid microvibration response was not obtainable; laterality was indicated in visual evoked potential and electroencephalographic studies, and the remaining evoked potentials demonstrated normal responses. The results obtained from the brainstem reflex (photo-evoked eyelid microvibration) suggest that the pathologic focus of Fisher syndrome is located in the midbrain, particularly in the pretectum. It is expected that the combined use of these electrophysiologic techniques may facilitate differentiation between Fisher and Guillain-Barré syndromes.     

Miller Fisher syndrome: clinical and electrophysiologic evidence of peripheral origin in 10 cases

Clinical and electrophysiologic data recorded in patients with Fisher syndrome characterized by ophthalmoplegia, ataxia, and areflexia are presented. Cases with limb weakness or pleocytosis in the CSF were excluded, according to Fisher. Ten patients were selected. All had hand and foot numbness. A large amount of protein without cell reaction was found during the third week of illness in serial CSF examinations. EMGs showed very slight limb involvement without spontaneous activity, and in most cases, facial muscles exhibited a denervation pattern. Distal motor nerve conduction velocity on limbs and F wave latencies were normal, whereas the sensory nerve action potentials were altered in all but one case when tested (seven out of eight cases). By means of blink reflex study performed in four patients, no significant pattern of brainstem dysfunction was discovered. The authors discuss the preeminent role of peripheral nerve lesions with regard to the ataxia and ophthalmoplegia.     

Familial Miller Fisher syndrome

Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia. Several reports of familial Guillain-Barré syndrome have been reported, indicating a possible underlying genetic and/or environmental predisposition to the development of Guillain-Barré syndrome. A familial association in Miller Fisher syndrome has not previously been described in the literature. We report 2 cases of Miller Fisher syndrome presenting simultaneously in siblings, with a review of recent relevant literature.     

Miller Fisher syndrome in infancy

Miller Fisher syndrome (MFS) is characterized by the triad of ataxia, areflexia and ophthalmoplegia. It is exceptional for infants to be involved. Two infants, aged 11 and 16 months, developed acute-onset MFS. Both patients had prodromal upper respiratory tract infection. Pupillary responses to light, strength and sensation modalities were preserved. One patient was lethargic for a day; the electroencephalogram disclosed slightly slow background activity that later became normal. The other received high-dose intravenous immunoglobulins for 5 consecutive days starting at once on admission; within the next 7 days he became asymptomatic. Increased cerebrospinal fluid protein content and delayed nerve conduction studies with prolonged distal latencies were encountered in both patients.     

Clinical and electrophysiological findings in two cases of Miller Fisher syndrome

Clinical, radiological and electrophysiological data in two patients with ‘Miller Fisher syndrome’ (MFS), characterized by ataxia, ophthalmoplegia and areflexia are reported. Of the many tests performed only the electrophysiological findings provided any clue to the site of the lesions and the structure involved, showing a significant pattern of brainstem dysfunction. The authors discuss the role of central and peripheral lesion theory in the light of these data and stress that electrophysiological findings lend considerable weight to the former and support the hypothesis that MFS should be recognize as a distinct clinical entity.

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Sommario Sono riportati i dati clinici, radiologici ed elettrofisiologici di due pazienti con sindrome di Miller Fisher (SMF), caratterizzata da atassia, oftalmoplegia ed areflessia. Di tutte le indagini eseguite solo quelle elettrofisiologiche trofisiologiche hanno fornito indizi sulla sede anatomica delle lesioni e sulle strutture coinvolte, evidenziando un quadro significativo di alterazioni del troncoencefalo. Gli autori discutono il ruolo delle teorie centrale e periferica alla base di questi dati e sottolineano che le informazioni elettrofisiologiche avvalorano la prima delle due ed indicano la necessità di riconoscere nella SMF una entità clinica distinta.

     

The immunopathogenesis of Miller Fisher syndrome

Over the past decade, remarkable progress has been made in our understanding of the pathogenesis of Miller Fisher syndrome (MFS), a clinical variant of Guillain Barré syndrome (GBS). MFS comprises the clinical triad of ataxia, areflexia and ophthalmoplegia. It is associated with acute-phase IgG antibodies to GQ1b and GT1a gangliosides in over 90% of cases which are highly disease specific. Like GBS, MFS is a post-infectious syndrome following diverse infections, but particular attention has been paid to its association with Campylobacter jejuni enteritis. Serostrains of C. jejuni isolated from infected patients bear ganglioside-like epitopes in their lipopolysaccharide core oligosaccharides, which elicit humoral immune responses exhibiting molecular mimicry with GQ1b/GT1a gangliosides. These antibodies are believed to be the principal cause of the syndrome and physiological studies aimed at proving this have focused on the motor-nerve terminal as a potential site of pathogenic action. This review describes these findings and formulates a pathogenesis model based on our current state of knowledge.     

Corticobulbar dysfunction in the Miller Fisher syndrome

The Miller Fisher syndrome is an immunologically mediated condition with minimal motor manifestations. We describe a case showing mild reversible dysarthria and weak lingual movements with complete recovery over 2 months. Transcranial magnetic stimulation studies give an evidence of a reversible corticobulbar conduction abnormality which resolved with clinical improvement.     

Anti-ganglioside complex antibodies in Miller Fisher syndrome

Background

Some ganglioside complexes (GSCs) are target antigens for serum antibodies in patients with Guillain–Barré syndrome (GBS). Anti‐GSC antibodies may be associated with particular clinical features of GBS.

Objective

To investigate antibodies to GSCs in the sera of patients with Miller Fisher syndrome (MFS) characterised by elevation of the IgG anti‐GQ1b antibody.

Results

In all, 7 of 12 (58%) consecutive patients with MFS were found to have IgG antibodies to GSCs containing GQ1b, of whom 5 had IgG antibodies to GQ1b‐GM1 complex (GQ1b/GM1) and 2 had antibodies to GQ1b/GD1a; 4 of 5 patients without sensory symptoms had anti‐GQ1b/GM1 antibodies.

Conclusions

At least three different specificities in MFS‐associated antibodies, GQ1b‐specific, anti‐GQ1b/GM1‐positive and anti‐GQ1b/GD1a‐positive, were observed. In patients with MFS not only GQ1b itself but also clustered epitopes of GSCs, including GQ1b, may be considered to be prime target antigens for serum antibodies. A tendency to escape sensory disturbances is shown by anti‐GQ1b/GM1‐positive MFS.We recently reported that some ganglioside complexes (GSCs) are target antigens for serum antibodies in patients with Guillain–Barré syndrome (GBS), an acute immune‐mediated polyradiculoneuropathy, and suggested that anti‐GSC antibodies may be associated with particular clinical features of GBS.¹ Because glycolipids including gangliosides tend to form clustered complexes with cholesterols in lipid rafts in the plasma membrane,² anti‐GSC antibodies are likely to cause nerve dysfunction through binding to GSCs in lipid rafts in neuronal membranes.Miller Fisher syndrome (MFS) is characterised by a clinical triad of ophthalmoplegia, ataxia and areflexia, and is considered to be a variant of GBS.³ The presence of the IgG anti‐GQ1b antibody in serum is an excellent diagnostic marker for MFS.⁴ This antibody often cross reacts with GT1a^4,5 and is pathophysiologically associated with ophthalmoplegia or ataxia in MFS and GBS.^5,6,7 Thus, MFS is a clinically and serologically well‐defined syndrome with a pathophysiological mechanism similar to that of GBS, which suggests that patients with MFS may also have anti‐GSC antibodies. Here, we examined the serum samples of patients with MFS and found antibodies specific for a mixture of two gangliosides, including GQ1b or GT1a.     

Collier's sign in Miller Fisher syndrome]

Collier's sign is well known as unilateral or bilateral eyelid retraction due to midbrain lesions. This sign is usually caused by infarction, tumor, multiple sclerosis, neuro-degenerative disease, or encephalitis. We report a case of Miller Fisher syndrome (MFS) which demonstrated Collier's sign. A 54-year-old man developed ophthalmoplegia, ataxia, and areflexia two weeks after common cold-like symptoms. At the same time, bilateral upper eyelid retraction (Collier's sign) was remarkably observed. Serum anti-GQ1b antibody was positive. Albumino-cytologic dissociation was seen at two weeks after onset. We treated him with high dose intravenous immunogloblins (IVIg) for five days. There was remarkable improvement after the administration of IVIg, and there was a complete recovery from his eyelid retraction. All his symptoms of MFS also disappeared. The eyelid retraction of Collier's sign has been reported to occur with lesions in the rostral midbrain and posterior commissure. Therefore, Collier's sign in this patient suggested central nervous system involvement in the MFS. To our knowledge, this is the first report of MFS associated with Collier's sign.     

Miller Fisher综合征14例报道

目的:分析14例Miller Fisher综合征的临床特点和预后。方法:回顾性分析1998年1月至2007年3月我院收治的14例Miller Fisher综合征患者,应用Microsoft Access 2003建立数据库,分析患者的各种症状、体征和各项检查和预后。结果:病前感染者11例,其中肠道感染8例,双侧动眼神经损害14例,眼内肌的损害7例,对光反射消失5例,共济失调9例,头晕7例,腱反射减低12例,肌力减退7例,周围神经损害5例,病理征3例,蛋白-细胞分离12例,影像学异常2例,肌电图改变7例。结论:Miller Fisher综合征临床症状复杂,可在经典的三联征基础上伴有其他体征,也可仅有其中的两联征,预后较好。     

Miller Fisher syndrome and Haemophilus influenzae infection

OBJECTIVE: To examine the association between Miller Fisher syndrome (MFS) and antecedent Haemophilus influenzae infection. BACKGROUND: Little is known about agents in prior respiratory tract infection of MFS, whereas antecedent upper respiratory symptoms are frequent. H. influenzae is a major pathogen that can cause human respiratory tract infection. METHODS: The authors used ELISA to detect serum antibody against the bacterium in 70 consecutive patients with MFS and 110 with Guillain-Barré syndrome (GBS). RESULTS: Serum anti-H. influenzae IgG and IgM antibody activities were significantly higher in the MFS group than in age- and sex-matched patients with other neurologic diseases (n = 62) and normal control subjects (n = 82). The GBS group showed no significant increase in any class of antibody activities compared with control groups. Serologic evidence of recent infection was found in five (7%) of the patients with MFS and two (2%) of 110 patients with GBS, all of whom had a history of antecedent respiratory tract infection. They frequently showed ophthalmoplegia, but other neurologic features were not remarkable. Serum anti-GQ1b IgG antibody that had cross-reactivity with GT1a ganglioside was detected in six of these seven patients. Thin-layer chromatography with immunostaining showed that serum IgG from H. influenzae-seropositive patients with high anti-GQ1b and anti-GT1a IgG antibody titers bound to the lipopolysaccharide fraction extracted from the type b H. influenzae serostrain. These bands were also stained by anti-GT1a monoclonal antibody (GMR11), indicating that the lipopolysaccharide bears the GT1a epitope. CONCLUSIONS: These findings point to H. influenzae being an agent associated with MFS. Epitopic overlap between H. influenzae and human nerve tissue may be involved in the development of MFS much as GBS is associated with Campylobacter jejuni enteritis.     

Intravenous immunoglobulin therapy for Miller Fisher syndrome

We analyzed clinical recovery of 92 patients with Miller Fisher syndrome who had been treated with IV immunoglobulin (IVIg; n = 28), plasmapheresis (n = 23), and no immune treatment (n = 41). IVIg slightly hastened the amelioration of ophthalmoplegia and ataxia, but the times of the disappearances of those symptoms were similar among three groups. In Miller Fisher syndrome, IVIg and plasmapheresis seem not to have influenced patients' outcomes, presumably because of good natural recovery.