Patterns of sensory nerve conduction abnormalities in Fisher syndrome: More predominant involvement of group Ia afferents than skin afferents

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Abstract

Objective

To elucidate the features of sensory nerve involvement in Fisher syndrome (FS), this study extensively investigated sensory electrophysiology.

Methods

In 47 consecutive FS patients, results of sensory nerve conduction studies in the median, ulnar and sural nerves, soleus H-reflexes, and median or tibial somatosensory-evoked potentials (SEP) were reviewed. Because of the large effects of age on amplitude of sensory nerve action potentials (SNAP), we strictly defined reduction of SNAP amplitudes by using a nomogram which age and amplitude obtained from 87normal subjects.

Results

In routine nerve conduction studies, SNAP amplitude was reduced only in 32% of the patients, and conduction velocity was decreased in 2%. In contrast, soleus H-reflexes were frequently absent or reduced (67%). SEPs were abnormal only in 17%.

Conclusions

In FS, absent soleus H-reflexes are the most frequent electrophysiologic abnormalities, whereas SNAPs amplitudes are rarely affected. The pattern is characterized by predominant involvement of group Ia afferents with relatively preserved cutaneous afferents without evidence suggestive of demyelination.

Significance

The major targets of immune attack by anti-GQ1b antibodies in FS appear to be group Ia neurons in the dorsal root ganglia, and this is presumably responsible for ataxia and areflexia in FS.

Highlights

► This study elucidated electrophysiologic features of sensory nerve involvement in 47 patients with Fisher syndrome (FS). ► Major abnormalities included absent/reduced soleus H-reflexes with rarely reduced sensory nerve potentials, suggesting more predominant involvement of group Ia afferents than cutaneous afferents. ► Ataxia and areflexia in FS are presumably caused by immune attack by anti-GQ1b antibodies to group Ia neurons in the dorsal root ganglia in FS.

Introduction

Fisher syndrome (FS) is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia (Fisher, 1956). The disorder is considered a variant of Guillain–Barré syndrome (GBS), although the lesion site is still a matter of controversy (Ogawara et al., 2002, Mori and Kuwabara, 2011, Shahrizaila and Yuki, 2012). In the original paper, Miller Fisher himself postulated the presence of unusual peripheral lesions, indicating that “a unique, widespread and selective attack on the sensory neurons underlying postural adjustments must have occurred,” and that “one would have to postulate a very selective involvement of special sensory neurons subserving the stretch reflex” (Fisher, 1956).

Then, electrophysiologic studies in FS have shown that peripheral sensory nerve lesions; amplitudes of sensory nerve action potential (SNAPs) decreased in some, not all, patients (Durand et al., 2001, Fross and Daube, 1987, Jamal and Ballantyne, 1988, Sauron et al., 1984). However, the extent of decreases in SNAP amplitudes were mild-to-moderate, and unlikely to be responsible for prominent ataxia in FS. Furthermore, because of the rarity of the disorder, the number of examined patients was limited in these reports; up to 10 patients. More recently, H-reflex studies showed the absent responses with frequently normal SNAP amplitudes, suggesting selective involvement of group Ia afferents (Dachy et al., 2010, Kuwabara et al., 1999a, Kuwabara et al., 1999b), but again, the number of examine patients was small (3–10 patients) and therefore the data did not provide conclusive results.

One of the major problems in sensory nerve conduction studies is that because of the large effects of aging on SNAP amplitudes, it is difficult to define abnormally reduced amplitudes. Many previous studies have demonstrated influence of age on nerve conduction parameters, particularly SNAP amplitudes (Fujimaki et al., 2009, Trojaborg et al., 1992, Salerno et al., 1998, Tong et al., 2004). To overcome this problem, the use of nomogram of age and SNAP amplitudes is recommended (Fujimaki et al., 2009).

Serum anti-GQ1b IgG antibody levels are frequently elevated in patients with FS, and this antibody probably plays an important role in the pathophysiology of this disorder (Chiba et al., 1992, Ito et al., 2008). Histochemical studies have shown that large neurons of the dorsal root ganglia, possibly group Ia neurons, were immunostained with anti-GQ1b monoclonal antibody. Anti-GQ1b IgG antibody may thus be associated with ataxia in FS (Kusunoki et al., 1999). Based on the accumulated data, we hypothesize that in FS, group Ia neurons are primarily involved, and validated our electrophysiologic data of sufficient number of FS patients.

Section snippets

Subjects

This study included 47 consecutive patients with FS (28 men and 19 women), seen at a single University Hospital in Japan between 1990 and 2011. All patients had the triad of ophthalmoplegia, ataxia and areflexia in 1–2 weeks, or the two symptoms of the triad with positive anti-GQ1b antibodies. All patients had acute ophthalmoplegia, ataxia and areflexia or the two symptoms with positive anti-GQ1b antibodies. Patients complicated by Guillain–Barré syndrome (n = 3) or Bickerstaff encephalitis (n = 3)

Clinical profiles

Table 1 shows the clinical profiles of the 47 FS patients. 96 percent had antecedent illnesses; 80% upper respiratory infectious symptoms only, 4% diarrhea only, and 4% both. Sensory impairment was infrequent; 23% had decreased in vibratory sensation, and 19% had reduced pin-prick sensation. Twenty seven percent of the patients were treated with immunoglobulin therapy.

Electrophysiology

Sensory nerve conduction study results are shown in Table 2. Routine motor nerve conduction studies and minimal F-wave latencies

Discussion

Our results show that the most frequent nerve conduction abnormality in FS is absent soleus H-reflex, and routine sensory nerve conduction studies are only occasionally abnormal. The findings are consistent with clinical data; FS patients invariably show areflexia, but rarely sensory loss, as confirmed in the present study. Sensory nerve conduction velocities are normal, and therefore there is no evidence suggestive of sensory nerve demyelination in FS. Moreover postural body sway analyses

Acknowledgments

We thank Dr. Funakoshi, Dokkyo University, for measuring anti-ganglioside antibodies. This study was supported in part by a Grant for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan (S.K.).

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