Miller Fisher anti-GQ1b antibodies: α-Latrotoxin–like effects on motor end plates

In the Miller Fisher syndrome (MFS) variant of the Guillain-Barré syndrome, weakness is restricted to extraocular muscles and occasionally other craniobulbar muscles. Most MFS patients have serum antibodies against ganglioside type GQ1b of which the pathophysiological relevance is unclear. We examined the in vitro effects of MFS sera, MFS IgG, and a human monoclonal anti-GQ1b IgM antibody on mouse neuromuscular junctions (NMJs). It was found that anti-GQ1b antibodies bind at NMJs where they induce massive quantal release of acetylcholine from nerve terminals and eventually block neuromuscular transmission. This effect closely resembled the effect of the paralytic neurotoxin α-latrotoxin at the mouse NMJs, implying possible involvement of α-latrotoxin receptors or associated downstream pathways. By using complement-deficient sera, the effect of anti-GQ1b antibodies on NMJs was shown to be entirely dependent on activation of complement components. However, neither classical pathway activation nor the formation of membrane attack complex was required, indicating the effects could be due to involvement of the alternative pathway and intermediate complement cascade products. Our findings strongly suggest that anti-GQ1b antibodies in conjunction with activated complement components are the principal pathophysiological mediators of motor symptoms in MFS and that the NMJ is an important site of their action. Ann Neurol 1999;45:189–199     

Concanavalin A inhibits pathophysiological effects of anti-ganglioside GQ1b antibodies at the mouse neuromuscular synapse

Anti-GQ1b antibodies are present in the Miller Fisher syndrome (MFS), a monophasic neuropathy characterized by ataxia, areflexia, ophthalmoplegia, and sometimes cranial muscle weakness. We have previously shown, at the mouse neuromuscular junction (NMJ) ex vivo, that anti-GQ1b antibodies, through complement classic pathway activation, block synaptic transmission in a way that resembles the effect of the pore-forming alpha-latrotoxin (alphaLTx). In order to clarify the mechanism of these alphaLTx-like effects, including possible involvement of the alternative and mannose-binding protein complement pathways, we studied the effects of concanavalin A (ConA), a lectin known to block the action of alphaLTx, immunoglobulins, and early complement components. With electrophysiological, immunohistological, and bioassay experiments, we showed that the alphaLTx-like effects of anti-GQ1b antibody and complement were inhibited by pre- and coincubation with ConA. However, ConA was not able to inhibit evolution of alphaLTx-like effects when coincubated upon addition of complement at NMJs that had already bound anti-GQ1b antibody. Our data suggest that the mannose-binding protein pathway is not involved in the alphaLTx-like effect and that the inhibiting effect of ConA principally arises through interference with presynaptic binding of anti-GQ1b antibody. In control experiments, ConA prevented the neuroexocytotic effects of alphaLTx, indicating that alphaLTx receptors were inhibited under these conditions. We conclude that, although the physiological effects at the NMJ of anti-GQ1b antibody and alphaLTx are very similar, the activity of anti-GQ1b antibody is not mediated through activation of alphaLTx receptors, but rather is caused by direct presynaptic membrane damage through classic complement pathway activation.     

Detection and prevalence of alpha-latrotoxin-like effects of serum from patients with Guillain-Barré syndrome

Anti-GQ1b antibodies are associated with the Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome (GBS). In the ex vivo mouse diaphragm, anti-GQ1b-positive MFS serum induces muscle fiber twitching, a temporary dramatic increase of spontaneous quantal acetylcholine release, and transmission blockade at neuromuscular junctions (NMJs). These effects resemble those of alpha-latrotoxin (alpha-LTx) and are induced by antibody-mediated activation of complement. We developed an assay for detection of the alpha-LTx-like effect, using muscle fiber twitching as indicator. We tested 89 serum samples from GBS, MFS, and control subjects, and studied correlations with clinical signs, anti-ganglioside antibodies, micro-electrode physiology, and complement deposition at NMJs. Twitching was observed with 76% of the MFS and 10% of the GBS samples. It was associated with ophthalmoplegia and anti-GQ1b antibodies in patients, and with increased spontaneous acetylcholine release and C3c-deposition at mouse NMJs. This study strongly suggests that antibodies to GQ1b (with cross-reactivity to related gangliosides) are responsible for the alpha-LTx-like activity. The twitching assay is an efficient test for detection of this effect, and allows for screening of large numbers of samples and modifying drugs.     

Combined pre- and postsynaptic action of IgG antibodies in Miller Fisher syndrome

BACKGROUND: Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome, is associated with the presence of neuromuscular blocking antibodies, some of which may be directed at the ganglioside GQ1b. MATERIALS AND METHODS: The authors investigated the in vitro effects of serum and purified immunoglobulin (Ig) G in a total of 11 patients with typical MFS during active disease, and in three of those patients after recovery. From one patient's serum, we prepared an IgG fraction enriched in anti-GQ1b antibodies by affinity chromatography. For combined pre- and postsynaptic analysis, endplate currents were recorded by a perfused macro-patch clamp electrode. Postsynaptic nicotinic acetylcholine receptor channels were investigated by an outside-out patch clamp technique in cultured mouse myotubes. RESULTS: AllMFS-sera depressed evoked quantal release and reduced the amplitude of postsynaptic currents. Five of the 11 sera were additionally examined by outside-out patch clamp analysis and caused a concentration-dependent and reversible decrease in acetylcholine-induced currents. The time course of activation and desensitization of nicotinic acetylcholine receptor channels was not altered by MFS-IgG. Nine patients (82 %) were positive for anti-GQ1b antibodies in ELISA and dot-blot. The enriched anti-GQ1b antibody fraction had a similar effect as whole serum. After recovery from MFS, blocking activity was lost and sera originally positive for anti-GQ1b antibodies became negative. CONCLUSION: Circulating IgG antibodies induce both pre- and postsynaptic blockade and may play a pathogenic role in acute MFS.     

Anti-disialosyl antibodies mediate selective neuronal or Schwann cell injury at mouse neuromuscular junctions

The human paralytic neuropathy, Miller Fisher syndrome (MFS) is associated with autoantibodies specific for disialosyl epitopes on gangliosides GQ1b, GT1a, and GD3. Since these gangliosides are enriched in synaptic membranes, anti-ganglioside antibodies may target neuromuscular junctions (NMJs), thereby contributing to disease symptoms. We have shown previously that at murine NMJs, anti-disialosyl antibodies induce an alpha-latrotoxin-like effect, electrophysiologically characterized by transient massive increase of spontaneous neurotransmitter release followed by block of evoked release, resulting in paralysis of the muscle preparation. Morphologically, motor nerve terminal damage, as well as perisynaptic Schwann cell (pSC) death is observed. The relative contributions of neuronal and pSC injury to the paralytic effect and subsequent repair are unknown. In this study, we have examined the ability of subsets of anti-disialosyl antibodies to discriminate between the neuronal and glial elements of the NMJ and thereby induce either neuronal injury or pSC death. Most antibodies reactive with GD3 induced pSC death, whereas antibody reactivity with GT1a correlated with the extent of nerve terminal injury. Motor nerve terminal injury resulted in massive uncontrolled exocytosis with paralysis. However, pSC ablation induced no acute (within 1 h) electrophysiological or morphological changes to the underlying nerve terminal. These data suggest that at mammalian NMJs, acute pSC injury or ablation has no major deleterious influence on synapse function. Our studies provide evidence for highly selective targeting of mammalian NMJ membranes, based on ganglioside composition, that can be exploited for examining axonal-glial interactions both in disease states and in normal NMJ homeostasis.     

C5 inhibitor rEV576 protects against neural injury in an in vitro mouse model of Miller Fisher syndrome

Guillain-Barré syndrome and its clinical variants, including the anti-GQ1b ganglioside-mediated Miller Fisher syndrome (MFS), comprise the world's leading cause of acute neuromuscular paralysis. Presently, no specific drug therapies exist. The complement cascade, which is activated in these patients, forms an attractive drug target. In this study, we tested whether the complement C5-inhibiting recombinant protein, rEV576, was able to prevent neural injury in a previously developed in vitro mouse model for MFS. Mouse hemidiaphragm preparations were treated with anti-GQ1b antibody and normal human serum as a source of complement with added rEV576 or control protein. Immunohistology in control tissue showed deposition of C3c and membrane attack complex at neuromuscular junctions (NMJs), along with terminal motor axonal neurofilament degradation as well as ethidium homodimer-2 staining showing perisynaptic Schwann cell (pSC) injury. Electrophysiological and functional analyses showed block of synaptic transmission at the NMJ after an initial period of a dramatically high level of asynchronous acetylcholine release. In tissue treated with rEV576, all these indicators of motor neuronal damage were absent, except for the presence of C3c, indicating effective inhibition of C5. These results demonstrate that rEV576 effectively prevents development of neuronal and pSC damage in experimental murine neuropathy.     

IgM anti-GQ1b monoclonal antibody inhibits voltage-dependent calcium current in cerebellar granule cells

Miller–Fisher syndrome (MFS), which is known to be associated with anti-GQ1b antibodies and to cause ataxia, is a variant of an acute inflammatory neuropathy. However, the pathogenic role of anti-GQ1b antibodies remains unclear. In this study, we investigated the effects of mouse IgM anti-GQ1b monoclonal antibody (IgM anti-GQ1b mAb) on the spontaneous muscle action potential of a rat spinal cord-muscle co-culture system and on the voltage-dependent calcium channel (VDCC) current in cerebellar granule cells and Purkinje cells using the whole-cell patch clamp technique. The frequency of spontaneous muscle action potential of the innervated muscle cells was transiently increased by IgM anti-GQ1b mAb and then was blocked completely, which was the same finding as reported previously. Moreover, the cerebellar granule cell VDCC current was decreased by 30.76 ± 7.60% by 5 μg/mL IgM anti-GQ1b mAb, whereas IgM anti-GQ1b mAb did not affect the VDCC current in cerebellar Purkinje cells. In immunocytochemistry, IgM anti-GQ1b mAb stained the whole cell surface of cerebellar granule cells, but not that of Purkinje cells. Therefore, the clinical symptoms of Miller–Fisher syndrome, such as cerebellar-like ataxia, may be explained by the inhibitory effects of anti-GQ1b antibodies on VDCC current in cerebellar granule cells.     

Rab3A deletion selectively reduces spontaneous neurotransmitter release at the mouse neuromuscular synapse

Rab3A is a synaptic vesicle-associated GTP-binding protein thought to be involved in modulation of presynaptic transmitter release through regulation of vesicle trafficking and membrane fusion. Electrophysiological studies at central nervous system synapses of Rab3A null-mutant mice have indicated that nerve stimulation-evoked transmitter release and its short- and long-term modulation are partly dependent on Rab3A, whereas spontaneous uniquantal release is completely independent of it. Here, we studied the acetylcholine (ACh) release at the neuromuscular junction (NMJ) of diaphragm and soleus muscles from Rab3A-deficient mice with intracellular microelectrode methods. Surprisingly, we found 20-40% reduction of spontaneous ACh release but completely intact nerve action potential-evoked release at both high- and low-rate stimulation and during recovery from intense release. The ACh release induced by hypertonic medium was also unchanged, indicating that the pool of vesicles for immediate release is unaltered at the Rab3A-deficient NMJ. These results indicate a selective role of Rab3A in spontaneous transmitter release at the NMJ which cannot or only partly be taken over by the closely related Rab3B, Rab3C, or Rab3D isoforms when Rab3A is deleted. It has been hypothesized that Rab3A mutation underlies human presynaptic myasthenic syndromes, in which severely reduced nerve action potential-evoked ACh release at the NMJ causes paralysis. Our observation that Rab3A deletion does not reduce evoked ACh release at any stimulation rate at the mouse NMJ, argues against this hypothesis.     

Recent developments in Miller Fisher syndrome and related disorders

PURPOSE OF REVIEW: Miller Fisher syndrome is a localized variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, areflexia and ataxia. Bickerstaff's brainstem encephalitis is a related syndrome in which upper motor neurone features accompany the classic triad. Anti-GQ1b antibodies are uniquely found in both conditions and are believed to be pathogenic. RECENT FINDINGS: Infectious illnesses usually precede Miller Fisher syndrome. The clearest associations have been described with Haemophilus influenzae and Campylobacter jejuni infection. Raised cerebrospinal fluid protein is seen in 60% of patients, but clinical features and anti-GQ1b antibody testing are diagnostically more informative. Experimental studies demonstrating complement-dependent neuromuscular block may be relevant to the clinical pathophysiology of Miller Fisher syndrome. Recent neurophysiological studies suggest abnormal neuromuscular transmission occurs in some cases of Miller Fisher syndrome and Guillain-Barré syndrome. Recent mouse models have demonstrated that presynaptic neuronal membranes and perisynaptic Schwann cells are targets for anti-GQ1b antibody attack. The elimination of antiganglioside antibodies from the circulation through specific immunoadsorption therapy has the potential to ameliorate the course of Miller Fisher syndrome. This condition is typically a benign, self-limiting illness. Both plasmapheresis and intravenous immunoglobulin may be employed as treatment, especially in cases of Bickerstaff's brainstem encephalitis or those with overlapping Guillain-Barré syndrome. SUMMARY: Anti-GQ1b antibody testing has allowed clinicians to develop a greater understanding of the spectrum of Miller Fisher syndromes and to refine clinical diagnoses in patients with unusual presentations. Experimental studies strongly suggest anti-GQ1b antibodies are pathogenic, which in principle should direct treatments towards antibody neutralization or elimination.     

Miller Fisher syndrome is associated with serum antibodies to GQ1b ganglioside.

A recent report described serum anti-GQ1b ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barré syndrome (GBS). Four consecutive cases of MFS all had high titre anti-GQ1b antibodies which were absent from all control sera including those of patients with GBS.     

Total ocular akinesis: Miller Fisher or Guillain-Barré syndrome?

Total, bilateral ophthalmoplegia is very rare. More than 50% of cases are Miller Fisher (MFS) and Guillain-Barré (GBS) syndromes. There is a correlation of MFS with anti-GQ1b antibodies. High levels of GQ1b gangliosides are found in myelin sheathes of cranial nerves supplying the extraocular muscles. This may explain the association of anti-GQ1b antibodies with ophthalmoplegia. Anti-GQ1b were also found in cases of GBS accompanied by ophthalmoplegia, atypical MFS (MFS without ataxia), MFS/GBS overlap syndromes and Bickerstaff brainstem encephalitis. This has led some authors to classify them as 'anti-GQ1b syndromes'. In this article we describe a diagnostically difficult case of a patient with a very rare, total bilateral paralysis of all ocular muscles, accompanied by bilateral ptosis, diminished tendon reflexes of upper extremities, paresis and hypoesthesia of the left upper extremity.     

Acute bilateral mydriasis associated with anti-GQ1b antibody

Miller Fisher syndrome (MFS) is an autoimmune neuropathy characterized by external ophthalmoplegia, ataxia and areflexia. Mydriasis is present in 35% of typical MFS. We report five patients with acute bilateral mydriasis, either isolated or associated with external ophthalmoplegia for which the presumed diagnosis of “atypical MFS” was confirmed by the positivity of anti-GQ1b antibodies. Acute bilateral mydriasis raises important differential diagnoses in clinical practice. This report demonstrates that acute mydriasis can be autoimmune mediated and that anti-GQ1b antibodies are useful to confirm the diagnosis in unexplained cases.     

Severely impaired neuromuscular synaptic transmission causes muscle weakness in the Cacna1a-mutant mouse rolling Nagoya

The ataxic mouse rolling Nagoya (RN) carries a missense mutation in the Cacna1a gene, encoding the pore-forming subunit of neuronal Ca(v)2.1 (P/Q-type) Ca2+ channels. Besides being the predominant type of Ca(v) channel in the cerebellum, Ca(v)2.1 channels mediate acetylcholine (ACh) release at the peripheral neuromuscular junction (NMJ). Therefore, Ca(v)2.1 dysfunction induced by the RN mutation may disturb ACh release at the NMJ. The dysfunction may resemble the situation in Lambert-Eaton myasthenic syndrome (LEMS), in which autoantibodies target Ca(v)2.1 channels at NMJs, inducing severely reduced ACh release and resulting in muscle weakness. We tested neuromuscular function of RN mice and characterized transmitter release properties at their NMJs in diaphragm, soleus and flexor digitorum brevis muscles. Clinical muscle weakness and fatigue were demonstrated using repetitive nerve-stimulation electromyography, grip strength testing and an inverted grid hanging test. Muscle contraction experiments showed a compromised safety factor of neuromuscular transmission. In ex vivo electrophysiological experiments we found severely impaired ACh release. Compared to wild-type, RN NMJs had 50-75% lower nerve stimulation-evoked transmitter release, explaining the observed muscle weakness. Surprisingly, the reduction in evoked release was accompanied by an approximately 3-fold increase in spontaneous ACh release. This synaptic phenotype suggests a complex effect of the RN mutation on different functional Ca(v)2.1 channel parameters, presumably with a positive shift in activation potential as a prevailing feature. Taken together, our studies indicate that the gait abnormality of RN mice is due to a combination of ataxia and muscle weakness and that RN models aspects of the NMJ dysfunction in LEMS.     

IgM monoclonal antibody against terminal moiety of GM2, GalNAc-GD1a and GalNAc-GM1b from a pure motor chronic demyelinating polyneuropathy patient: effects on neurotransmitter release

We describe a patient with a pure motor chronic demyelinating polyneuropathy with an IgM monoclonal component showing anti-GM2, GalNAc-GD1a and GalNAc-GM1b reactivity whose common epitope appears to be -[GalNAcbeta1-4Gal(3-2alphaNeuAc)beta1]. We used intracellular recording to study how IgM from this patient affected neurotransmitter release in the mouse diaphragm in vitro.Adding serum (and specifically, the purified monoclonal IgM component) blocked the nerve-evoked response in both quantal content and evoked endplate potential (EPP) amplitude in a complement-independent and reversible manner. The IgM increased the frequency of spontaneous miniature endplate potentials (MEPPs) in a complement-dependent and reversible manner but had no effect on MEPP amplitude.     

Effects of phospholipids on antiganglioside antibody reactivity in GBS

Serum antibody activities to mixtures of a ganglioside and various phospholipids were compared with those to a ganglioside alone in 30 anti-GM1 IgG-positive GBS patients and 30 anti-GQ1b IgG-positive Miller Fisher syndrome (MFS) patients. Anti-GM1-positive sera had higher antibody reactivities against a mixture of GM1 and several phospholipids including PA, PI and PS, than against GM1 alone. In contrast, in case of anti-GQ1b antibody, no phospholipid provided significant enhancement. Sphingomyelin provided decrease of the activity for both anti-GM1 and anti-GQ1b IgG. The effects of phospholipids must be considered to determine the pathogenetic role of antiganglioside antibodies in GBS and MFS.     

The relation of clinical symptoms and anti-ganglioside antibodies to MEPPs frequency increase in 8 cases of variant type Guillain-Barré syndrome

Many patients with variant forms of Guillain-Barré syndrome (vGBS) associated with anti-ganglioside antibodies, including Miller Fisher syndrome (MFS), sometimes exhibit miniature endplate potential (MEPP) frequency increases (MFI, described as alpha-latrotoxin-like effects in a previous report) and the factor to produce this effect is present in their sera. MFI-positive sera increase the frequency of MEPPs, then block neuromuscular transmission at the mouse neuromuscular junction. A connection between this effect at the neuromuscular junction and some vGBS symptoms is suspected. We measured MFI directly at several points during the clinical course of 8 vGBS patients who had various symptoms and courses. Six patients had confirmed MFI and this activity decreased with convalescence. In 3 clinically mild cases, we were able to elicit MFI using normal serum to supply complement after exposure to the patient's serum. The anti-GQ1b/GT1a IgG titer, the extent of ophthalmoplegia and the extent of MFI were significantly correlated. They did not correlate with the severity of limb weakness or the occurrence of respiratory failure. These results support the hypothesis that MFI caused by anti-ganglioside antibodies is the pathogenic mechanism responsible for ophthalmoplegia in vGBS; different mechanisms or antibodies may explain limb weakness and respiratory failure. Furthermore, MFI may be an important indicator of how serum injures the nerve terminals. The symptoms of vGBS may result from multiple pathogenic factors.     

Acute isolated ophthalmoplegia with anti-GQ1b antibodies

Ophthalmoplegia without ataxia, areflexia or both has been designated as atypical Miller Fisher syndrome (MFS) or acute ophthalmoplegia (AO). This entity, first reported by Chiba et al. is associated with anti-GQ1b IgG antibodies.We report a patient with isolated acute ophthalmoplegia with high titer of anti-GQ1b IgG antibody activity in the acute phase in whom treatment with intravenous immunoglobulin (IVIg) led to the clinical recovery and the decrease in antibody titer.     

Features of sensory ataxic neuropathy associated with anti-GD1b IgM antibody

Some reports have called sensory ataxic neuropathy (SAN) associated with IgM antibody against b-series gangliosides a chronic form of Miller Fisher syndrome (MFS), but this has yet to be established. We examined five patients with SAN and eight patients with IgG anti-GQ1b-positive MFS. Only one patient with SAN complained of diplopia, whose ocular movement was not limited. The other four patients had neither diplopia nor limitation of ocular movement. All the SAN patients had severe deep sense impairment, whereas one patient with MFS showed only mild vibratory sense impairment. All sera from the SAN patients had remarkably high IgM antibody titers to the b-series gangliosides GD3, GD2, GD1b, GT1b, GQ1b, GQ1b alpha, fucosyl-GD1b, and alpha galactosyl [alpha fucosyl] GD1b. An absorption study confirmed that the anti-GQ1b antibodies cross-reacted with GD3, GD2, GD1b, and GT1b. In contrast, only two samples from the MFS patients had IgG antibody to GD3, and no sample reacted with GD2, GD1b, or GT1b. SAN has different clinical or serological features from MFS, and therefore is not a chronic form of it.     

Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse

Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity‐dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A₁R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M₂ action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin‐related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. © 2014 Wiley Periodicals, Inc.     

Clinical presentation and outcome of Guillain-Barré and related syndromes in relation to anti-ganglioside antibodies.

We correlated the clinical features of 78 patients with Guillain-Barré syndrome (GBS) or related variants, with the presence of serum antibodies to the gangliosides GM1, GM2, GD1a, GD1b and GQ1b in order to determine whether these antibodies may influence the clinical presentation or outcome of GBS. Sixty-three patients had typical GBS (81%), nine a pure motor form (11%), three a paraparetic form (4%), and three had Miller Fisher syndrome (MFS). IgG or IgM (or both) anti-ganglioside antibodies were found by ELISA in 37% of patients, including 36% with typical, 33% with pure motor and 100% with MFS. Beside the constant occurrence of anti-GQ1b antibodies in patients with MFS (P<0.00001), the other clinical forms were not associated with a specific anti-ganglioside reactivity. Anti-GM1 and anti-GD1a antibodies tended to be associated with a worse disability at 6 month than other or no reactivity and, similarly to anti-GM2 antibodies, with a more frequent respiratory impairment. Anti-GM2 and anti-GD1b antibodies were always associated with typical GBS and, in all but one patient, with a complete recovery; still they were found in only 13 and 3%, respectively, of the patients with this presentation. Anti-GQ1b antibodies, though always associated with ophthalmoplegia and ataxia in both MFS and GBS, were found in only 36 and 26%, respectively, of patients with these symptoms. Even if different anti-ganglioside antibodies tend to be associated with some clinical features possibly suggesting that they may influence the clinical presentation or outcome, with the exception of anti-GQ1b antibodies for ophthalmoplegia and ataxia, they do not permit to predict the clinical presentation or outcome in individual patients.