Anti-GQ1b antibody syndrome …

Alexandru C Barboi MD FACP

Neuroimmunology

Updated 10.23.2024
Released 12.03.2010
Expires For CME 10.23.2027

Anti-GQ1b antibody syndrome

Author: Alexandru C Barboi MD FACP

See Contributor Disclosures

Editor: Francesc Graus MD PhD

Anti-GQ1b antibody syndrome

In This Article

Quick Link

Introduction

Overview

Prior to the discovery of IgG antibodies against GQ1b, there were clinical variants that were considered linked to Guillain-Barré syndrome due to shared clinical features. The most notable are Miller Fisher syndrome, which is characterized by acute ophthalmoplegia, ataxia, areflexia, and Bickerstaff brainstem encephalitis, in which consciousness is also affected. Following the discovery of an association of GQ1b antibodies with Miller Fisher syndrome in 1992, other neurologic presentations with similar serological profiles emerged in the literature, including Bickerstaff brainstem encephalitis, acute ophthalmoplegia, optic neuropathy with disc swelling, acute ataxic neuropathy, pharyngeal-cervical-brachial weakness, and acute vestibular syndrome. In this article, the author discusses the current understanding behind the anti-GQ1b antibody syndrome.

Key points

	• GQ1b antibodies are a serological marker of Miller Fisher syndrome and Bickerstaff brainstem encephalitis but have been detected in other neurologic syndromes.
	• The overall prognosis is good even without immunotherapy in those patients who have typical Miller Fisher syndrome or acute ophthalmoplegia, but intravenous immunoglobulin (IVIg) or plasma exchange is recommended when there is altered consciousness, limb weakness, or bulbar palsy.
	• Important mimics to be excluded include brainstem syndromes of other etiologies and neuromuscular junction disorders. GQ1b antibody positivity in this context helps the differential diagnosis.
	• Miller Fisher syndrome and Bickerstaff brainstem encephalitis can occur in association with a COVID-19 infection and post COVID-19 vaccination.
	• Testing for serum antiganglioside antibodies outside of clearly defined and known associated phenotypes has an extremely low yield and is not recommended. CSF antiganglioside antibody assay provides no additional information and is not recommended.

Historical note and terminology

In 1951, Bickerstaff and Cloake described three patients who presented with prominent drowsiness followed by brainstem signs causing ophthalmoplegia, facial palsy, bulbar palsy, and ataxia following a prodrome of infective illness. The etiology of this condition was presumably like that of Guillain-Barré syndrome based on the presence of prodromal symptoms in all three patients, areflexia with CSF albuminocytologic dissociation in one patient, and subsequent recovery of neurologic symptoms in all three patients (03). Six years later, Bickerstaff extended his observations including an additional five patients with similar patterns of brainstem signs, emphasizing the benign outcomes in all but one patient, who died following a seizure (02). This condition has since been referred to as Bickerstaff brainstem encephalitis.

Miller Fisher syndrome was first described in 1956 by Charles Miller Fisher. He reported three patients who presented with a triad of total external ophthalmoplegia, ataxia, and areflexia after an upper respiratory tract infection (10). The presence of CSF albuminocytologic dissociation and antecedent infection likened Miller Fisher syndrome to Guillain-Barré syndrome.

In 1992, Chiba and colleagues identified IgG antibodies against ganglioside GQ1b in six patients with typical Miller Fisher syndrome (05). The GQ1b IgG antibodies were initially considered as a serological marker of Miller Fisher syndrome. However, the antibodies were also detected in patients with acute postinfectious ophthalmoplegia without ataxia, Guillain-Barré syndrome with ophthalmoplegia, and Bickerstaff brainstem encephalitis (56; 17). The latter findings supported the continuity between the two syndromes. Patients with milder clinical features, such as ophthalmoparesis without ataxia (54), or more extensive involvement with limb weakness (34), were also found to have GQ1b IgG serum antibodies. In view of the common serological profile shared by this group of patients, it has been referred to as "anti-GQ1b antibody syndrome" (46).

Clinical manifestations

Presentation and course

• Miller Fisher syndrome represents just one of the clinical presentations included in the term "anti-GQ1b antibody syndrome."

Presentation is typically seasonal, with fall (84%) and spring (16%) predominance. Patients with "anti-GQ1b antibody syndrome" can present with a range of neurologic features. The classical triad of ophthalmoplegia, ataxia, and areflexia continues to be the commonest presentation in Miller Fisher syndrome (10; 17). Ophthalmoplegia seems to be the most prevalent and consistent finding in Miller Fisher syndrome and can be the result of central or peripheral localizations (26). A central lesion is suggested by the presence of concomitant strabismus (ocular misalignment does not change according to the direction of gaze or which eye is fixating on the target), preservation of the Bell phenomenon, and adduction palsy, which is overcome by convergence (26). Acute concomitant strabismus in 13% of 84 patients with anti-GQ1b antibody associated ophthalmoplegia has been described and manifests most commonly as esotropia (26). Patients with a central lesion accounting for their ophthalmoplegia more frequently have spontaneous, gaze evoked, positional nystagmus and saccadic hypermetria compared to those with paralytic (peripheral) strabismus and are less likely to show ptosis or iridoplegia (26). Internuclear ophthalmoplegia was also described in the anti-GQ1b syndrome (26). Patients with peripheral lesions develop a relatively symmetrical external ophthalmoplegia (76%), but the condition can also be unilateral. Abduction deficit was the most common finding (33%). Similar findings can be seen in acute ophthalmoplegia without ataxia. Internal ophthalmoplegia is a frequent finding, particularly in patients exhibiting limb weakness and in Bickerstaff variants. Light-near dissociation has been reported. Optic nerve involvement may occur unilaterally or bilaterally and is almost always accompanied by disc edema (20).

Of note is that limb and gait “cerebellar-like ataxia” can also be the initial presenting symptoms and is accompanied in 75% of cases by distal limb loss of proprioception and negative Romberg sign (34). Common sensory complaints include paresthesias matched by reduced pin (7%) and vibratory sense (17%) (17). Aside from these two characteristic features, other clinical features are recognized. In a study of 50 consecutive patients with Miller Fisher syndrome there were signs of blepharoptosis (58%) and mydriasis (42%), both occurring frequently at the height of the illness (34) (see Clinical vignette case #1). Some patients were also noted to have facial (32%) and bulbar palsy (26%). Sensory symptoms are less frequent than would be expected given the gross ataxia. Although atypical, some patients with Miller Fisher syndrome may have a Babinski sign and rarely require ventilatory support (17). There have been additional reports on the development of delayed facial palsy in patients with Miller Fisher syndrome (47). In such instances, facial palsy develops after cardinal features of Miller Fisher syndrome have reached a nadir or started to improve.

The spectrum of anti-GQ1b antibody syndrome includes acute ophthalmoplegia, acute ptosis, acute mydriasis, acute oropharyngeal palsy, acute ataxic neuropathy (without ophthalmoplegia), optic nerve edema, and acute vestibular syndrome (27).

Patients with Bickerstaff brainstem encephalitis present not only with ataxia and ophthalmoplegia, but also features that suggest involvement of the CNS, such as altered levels of consciousness and brisk reflexes (02). Patients can also present with an overlap of the pharyngeal-cervical-brachial variant of Guillain-Barré syndrome (37). Atypical presentations of Bickerstaff brainstem encephalitis with only hypersomnolence and ataxia, without ophthalmoplegia, have also been reported and have been associated with the presence of GQ1b antibodies supporting the diagnosis (50). The area postrema syndrome, characterized by intractable nausea, vomiting, or hiccups has also been described in a small group of patients with Bickerstaff brainstem encephalitis; however, no GQ1b antibodies were detected in such cases (57). A paper from the GBS Classification Group proposed inclusive diagnostic criteria that can facilitate early diagnosis of variants of Miller Fisher syndrome (50).

A retrospective study reported the differences in clinical characteristics between GQ1b antibody-positive and antibody-negative Bickerstaff brainstem encephalitis. Compared to patients without antibodies, those with antibodies had more frequent preceding upper respiratory infection (70% vs. 20%) and paresthesias (44% vs. 0%), less frequent brain MRI abnormalities (8% vs. 50%), lower median CSF cell count (12.5/µL vs. 75.9/µL) lower median protein levels (63.5 mg/dL vs. 159 mg/dL), and shorter median time to get recovery of consciousness (10 days vs. 23 days), indicating that Bickerstaff brainstem encephalitis with GQ1b antibodies has homogeneous features (52).

Prognosis and complications

The functional outcome of patients with anti-GQ1b antibody syndrome is usually good in either typical Miller Fisher syndrome or Bickerstaff brainstem encephalitis. In Miller Fisher syndrome, patients tend to make a spontaneous recovery. Improvement in ataxia is reported to start at a median of 12 days (range, 3 to 41 days) after the onset, followed closely by improvement in ophthalmoplegia, median 15 days (range, 3 to 46 days). The median periods between the onset and complete recovery of ataxia and ophthalmoplegia were 32 days (range, 8 to 271 days) and 88 days (range, 29 to 165 days), respectively (34). Facial palsy may develop subsequently, even when ataxia or ophthalmoplegia have started to improve (47).

Although Miller Fisher syndrome can recur following an antecedent illness, when associated with anti-GQ1b antibodies, the outcome is favorable in most patients. In a study, recurrences occurred more frequently in patients with Miller Fisher syndrome or Bickerstaff brainstem encephalitis compared with those with Guillain-Barré syndrome (16). Symptoms and signs were less severe during relapses than during the initial episode in recurrent patients (16) (see Clinical vignette case #2).

Bickerstaff brainstem encephalitis is also associated with a good recovery, but increased mortality has been described (02; 37), which may be due to a central respiratory depression or secondary to complications such as a concurrent infection. The majority of patients will achieve complete remission by six months, but in a minority, symptoms of paresthesias, diplopia, or ataxia may persist (37).

Overlap can occur between Miller Fisher syndrome and Guillain-Barré syndrome as well as other variants including pharyngeal-cervical-brachial variant and Bickerstaff brainstem encephalitis. A study found the overlap syndrome to occur in 50% of pure Miller Fisher syndrome cases, typically within seven days of the onset of Miller Fisher syndrome. In cases where there is an overlap of Guillain-Barré syndrome the prognosis will depend on the severity of Guillain-Barré syndrome. Limb weakness can persist for those who have a severe axonal degeneration. Complications related to autonomic dysfunction such as cardiac arrhythmias should also be borne in mind, and close monitoring is warranted in the early stages of the illness. A case of Takotsubo cardiomyopathy associated with Bickerstaff brainstem encephalitis has been reported (43).

Clinical vignette

Below are two cases. Case 1 is a picture of eye movements recorded from a 39-year-old woman who developed total ophthalmoplegia and facial diplegia associated with GQ1b antibodies (see Case 1 figure). Case 2 is a 39-year-old man who developed a total of four episodes of Guillain-Barré syndrome or Miller Fisher syndrome.

Case 1: Eye movements with facial diplegia.

Eye movement disorders typical of Miller Fisher syndrome

This picture shows eye movement disorders typical of Miller Fisher syndrome characterized by symmetric almost total ophthalmoplegia with bilateral pupillary mydriasis associated with anti-GQ1b IgG antibodies. Note bilateral ptosis...

Case 2: Representative case of recurrent Guillain-Barré syndrome or Miller Fisher syndrome.

A 39-year-old man was admitted to the hospital with Miller Fisher syndrome in 2004, but he had two similar episodes that required hospitalizations in 1994 and 1998.

In February 1994, at 29 years of age, the patient was admitted to another hospital with a diagnosis of Guillain-Barré syndrome.

The patient had been well until two weeks before admission, when fever, vomiting, and diarrhea developed, followed by diplopia, bilateral leg weakness, tingling sensation in his left arm and bilateral legs, and dysphagia. He was initially treated with oral prednisolone 15 mg daily at a local clinic, but muscle weakness further progressed in all limbs, ultimately leading to a hospitalization to a local hospital. The patient was initially treated with intravenous high-dose methylprednisolone but soon transferred to another hospital where he was diagnosed with Guillain-Barré syndrome and started on immunoadsorption plasmapheresis followed by double filtration plasmapheresis, resulting in improvement. He was discharged on the 22nd hospital day with mild bilateral abducens palsy, hyporeflexia, and mild muscle weakness but his symptoms had resolved subsequently.

Four years later, in December 1998 at 33 years of age, the patient was readmitted to the same hospital with a similar episode. Two weeks before admission, sore throat and cough developed. Then he began to have diplopia, dizziness, and tingling sensation in the left hand and sole of the feet. On admission the patient had bilateral abducens palsy, ataxia, areflexia, mild weakness, and mild bulbar palsy. GQ1b IgG antibodies were detected in the serum. The patient was treated with four rounds of immunoadsorption plasmapheresis, resulting in resolution of his symptoms. On discharge he had mild horizontal diplopia and hyporeflexia, but the diplopia subsequently disappeared.

Six years later, in May 2004 at 39 years of age, the patient was admitted to our hospital with recurrence of Miller Fisher syndrome. One week before admission, sore throat and cough developed without fever. One day before admission, diplopia and tingling sensation in his left hand and leg developed. He also had severe anorexia and nausea. The next day dizziness, dysesthesia in the right hand, and retroorbital pain also developed. He was admitted to our hospital.

On examination the temperature was 37.0°C, the blood pressure 112/70 mm Hg, and the pulse 72 beats per minute. Physical examination was unremarkable. On neurologic examination the patient was alert and well oriented. His speech was normal. The pupils were 4.0 mm, equal, both reacted sluggishly to light. Both eyes were esotropic in primary position; there was bilateral abduction palsy, mild upward gaze palsy, and ptosis on the right. There was no nystagmus. The remainder of the function of the cranial nerves was intact, including the muscle power of the orbicularis oculi. He had mild weakness in his neck flexor, bilateral biceps brachii and triceps brachii, and left hip flexor; the grip strength was 29 kg on the right and 13 kg on the left. He complained of dysesthesias in the tips of the fingers of the left hand, but sensory examination was normal, including vibration and position sense. The deep tendon reflexes were diminished except the left biceps and triceps jerks, which were normal; the plantar response was flexor bilaterally. Coordination was intact in the upper limbs but mildly impaired in the left lower limb on heel-shin test. He was not able to walk due to truncal ataxia and severe nausea. The neck was supple.

The blood test results were unremarkable except elevated level of serum CRP (1.12 mg/dL). CSF examination on the day of admission (day 1) revealed one white blood cell/µL, with normal protein level (25 mg/dL). A brain MRI did not show abnormal enhancement along the affected cranial nerves. A nerve conduction study and electroencephalogram were unremarkable.

The patient was initially suspected as Miller Fisher syndrome or Guillain-Barré syndrome with ophthalmoplegia and he was started on IVIg (0.4 g/kg/day, 5 days) on day 1. The symptoms, including muscle weakness, had progressed for seven days and the right eye became midline fixed; however, after reaching the peak, the symptoms started improving, without additional immunotherapy. The follow-up CSF examination obtained on day 8 revealed 10 white blood cells/µL with elevated protein levels (51 mg/dL). The serum was positive for GQ1b IgG antibodies (1:3200) but negative for other IgG antibodies against GM1, GD1b, GD1a, GT1b, GM2, and GalNAc-GD1a; GT1a antibodies were not examined at that time. He was discharged on day 25, with mild right abduction palsy, which resolved subsequently.

Nine years later, in early March 2013 at 48 years of age, the patient was readmitted to our hospital with recurrent similar episode. Twelve days before admission, cough, sore throat, and low-grade fever developed. One day before admission on awakening he noticed diplopia and dysesthesias in the tips of all fingers and toes and perioral area. He was admitted to our hospital.

On examination the temperature was 38.4°C, the blood pressure 114/77 mm Hg, and the pulse 86 beats per minute. Physical examination was otherwise unremarkable. The patient was alert and well oriented. His speech was normal. There was bilateral ptosis (more affected on the right than the left). The pupils were 4.0 mm, equal, and both did not react to light. The eye movements were mildly restricted in all directions bilaterally with monocular nystagmus on the left eye on looking to the left. Muscle power of the orbicularis oculi was weak on both sides. Muscle strength was normal in all limbs. Sensory examination was unremarkable except mild reduction of vibration sense in the legs and subjective tingling sensation in his perioral area and distal parts of all limbs. Coordination was intact on finger-nose tests and heel-shin tests, but he was not able to walk without assistance. Romberg sign was negative. The deep tendon reflexes were diminished in all limbs.

The blood test results were unremarkable. CSF examination on admission (day 1) revealed one white blood cell/µL, with normal protein level (27 mg/dL), without CSF-restricted oligoclonal band detection. A brain MRI was normal. A nerve conduction study was unremarkable but H-reflex study showed decreased H/M amplitude ratio.

After admission the patient was started on IVIg. Ophthalmoplegia and limb ataxia progressed for 6 days, resulting in total ophthalmoplegia (mid-line fixed on both eyes) but after day 8 dysesthesias and ataxia started improving, followed by gradual improvement in ophthalmoplegia. The patient became able to walk independently on day 13 and he was discharged on day 18. On discharge ophthalmoplegia still persisted but eye movements had almost recovered on the last visit 51 days after the onset of Miller Fisher syndrome; areflexia remained diminished.

In the fourth episode both GQ1b IgG antibodies (1:6400) and GT1a IgG antibodies (1:12,800) were detected but there were no IgG antibodies against GM1, GD1b, GD1a, GT1b, GM2, and GalNAc-GD1a (< 1:100).

In summary, the patient developed four similar episodes compatible with a diagnosis of Guillain-Barré syndrome with ophthalmoplegia at the first episode and Miller Fisher syndrome in the subsequent ones. Although it is rare, recurrent Guillain-Barré syndrome or Miller Fisher syndrome can occur. In this patient, GQ1b antibodies were detected in three of three examined episodes, and GT1a antibodies were also found at high titers, concurrent with GQ1b antibodies in the fourth episode (but not examined in the other episodes). It is unclear whether IVIg hastened recovery in the last two episodes of typical Miller Fisher syndrome, in which spontaneous recovery is the rule, but we used IVIg because the patient had developed bulbar palsy and muscle weakness in the first two episodes.

Biological basis

Etiology and pathogenesis

Gangliosides are glycosphingolipids containing at least one sialic acid linked to a carbohydrate moiety. They are found everywhere in the body but are enriched in the outer layers of the neuronal membranes. Gangliosides are important for neuronal growth regulation, neurotransmission, neuronal differentiation, and repair (12; 27). One theory is that infectious agents that use gangliosides to evade the immune system lead to the production of anti-ganglioside antibodies (12).

A patient with typical Miller Fisher syndrome or Bickerstaff brainstem encephalitis generally presents with an antecedent episode prior to the onset of their neurologic symptoms. Epidemiological associations between Campylobacter jejuni and Haemophilus influenza infections have been established in patients with Miller Fisher syndrome, and a study looking at the serological evidence of infection in patients with Bickerstaff brainstem encephalitis or Miller Fisher syndrome found C jejuni and H influenza to be the two most common pathogens in this group of patients (17; 47). Molecular mimicry whereby the lipo-oligosaccharides of C jejuni isolated from patients with Miller Fisher syndrome or Bickerstaff brainstem encephalitis mimic the GQ1b has been demonstrated (21). Other mimics include the GQ1b-like lipo-oligosaccharide of H influenza isolated from a patient with Miller Fisher syndrome (14). Following the Zika virus epidemic in Latin America in 2016, there was a rise in the number of patients with Guillain-Barré syndrome. A report of 68 Colombian patients with Zika-associated Guillain-Barré syndrome described two cases with clinical features of Miller Fisher syndrome, expanding the possible microbial associations (48). Miller Fisher syndrome has been documented both after COVID-19 infection and after COVID-19 vaccination (36).

Immunohistochemical studies show that GQ1b is highly expressed in the extra-axial regions of the human oculomotor, trochlear, and abducens nerves as compared to other cranial nerves or the ventral and dorsal roots of the spinal cord (04). The neuromuscular junctions may be particularly vulnerable to autoantibody attack as they are outside the blood-nerve barrier. Of note, monoclonal GQ1b antibodies were shown to bind to the vast majority of motor endplates of human oculomotor muscles (28). In an animal model of Miller Fisher syndrome, monoclonal GQ1b antibody plus complement was shown to damage nerve terminals, resulting in the production of mitochondrial hydrogen peroxide that in turn activates Schwann cells (41). Using an in vitro cellular model consisting of co-cultured primary neurons and Schwann cells, the authors found that adenosine triphosphate (ATP) was also released by the injured neurons. The neuron-derived ATP acts as an alarm messenger for Schwann cells, inducing the activation of intracellular pathways and promoting nerve regeneration (40).

Postural body sway analysis results suggest that patients with Miller Fisher syndrome also have a dysfunctional proprioceptive afferent system, and the distinctive sensory ataxia is caused by the selective involvement of muscle spindle afferents. These muscle spindles contain specialized muscle fibers, which have motor innervations and are enriched with sensory endings. The neural components and intrafusal muscle fibers of these spindles may be important targets in Miller Fisher syndrome because they have also been labelled by monoclonal GQ1b antibodies in humans (28). The staining pattern suggests that the group 1a afferents in muscle spindles contain GQ1b. Another common neurophysiological finding in patients with Miller Fisher syndrome is an abnormal H-reflex. This finding cannot be explained by involvement of the muscle spindles in isolation (24). It is likely that impairment of the group 1a neurons in the dorsal ganglion also contributes to the ataxia and areflexia (42). In support of this is the finding that GQ1b is also expressed in some large neurons in the human dorsal root ganglia. Patients with Miller Fisher syndrome typically show recovery with no sequelae (34); one explanation could be reversible axonopathy of the group 1a fibers due to lengthening of the nodes of Ranvier and myelin splitting with no demyelination features.

In Bickerstaff brainstem encephalitis, the characteristic distinguishing clinical feature is altered levels of consciousness that is central in origin. It is postulated that the breakdown of the blood-brain barrier at vulnerable sites, such as the area postrema or blood-nerve barrier at the roots of the oculomotor cranial nuclei, allows access to GQ1b antibodies, which then bind to its related sites within the brainstem reticular formation; however, this course of events has yet to be confirmed. In a study the authors postulated that local or distant neurotoxic effects of endocytosed and retrogradely transported antiganglioside antibodies to the reticular activating system, which lies adjacent to oculomotor nerves in the brainstem, may account for the coma seen in Bickerstaff brainstem encephalitis (06).

In summary, the presumed pathogenetic mechanism in Miller Fisher syndrome and Bickerstaff brainstem encephalitis is as follows:

(1) Infection by a microorganism expressing GQ1b epitope triggers the production of GQ1b antibodies. IgG anti-GQ1b is pathogenic, whereas the role of IgM anti-GQ1b is unclear at this time.

(2) These antibodies bind to GQ1b, which are highly expressed on the oculomotor nerves, resulting in acute ophthalmoplegia and group 1a muscle spindles, producing acute ataxic neuropathy.

(3) Antiganglioside antibodies demonstrate cross-responsiveness: one antigen can produce antibodies that target multiple gangliosides to perhaps explain overlap syndromes: GT1a (GT1a-GD1a and GT1a-GQ1b) (12). In some patients, these antibodies can also bind to the reticular formation where GQ1b may be expressed, causing Bickerstaff brainstem encephalitis (55). In a reported review on antiganglioside antibodies in Guillain-Barré and Miller Fisher syndromes, the authors emphasized the presence of antibodies that specifically recognize a new conformational epitope formed by two different gangliosides (ganglioside complex), which can be detected in some patients with Guillain-Barré or Miller Fisher syndromes (23).

Given the good prognostic outcome of Miller Fisher syndrome, there are a few pathological studies available, but it is generally agreed that the pathology in Miller Fisher syndrome is dominantly peripheral (01), whereas overlap syndromes and Bickerstaff encephalitis also have central lesions (37; 17).

Differential diagnosis

Anti-GQ1b antibody syndrome should be differentiated from disorders manifesting with acute or subacute ophthalmoplegia or ataxia (27).

It is important to rule out a stroke in any patient who presents with an acute brainstem syndrome. Thiamine deficiency can mimic Bickerstaff brainstem encephalitis, especially when Wernicke encephalopathy develops with ophthalmoplegia, ataxia, and short-term memory loss (which may be interpreted as drowsiness).

Central demyelinating conditions such as acute disseminated encephalomyelitis and multiple sclerosis can also present with a constellation of brainstem signs that can cause a diagnostic dilemma. The presence of ophthalmoplegia along with good recovery of clinical symptoms and signs, including resolution of abnormal lesions on brain imaging, would favor Bickerstaff brainstem encephalitis. In multiple sclerosis, the future course might involve further neurologic symptoms and signs (relapsing remitting form) or a progressive deterioration (primary progressive form). Pituitary apoplexy can present with a headache, mental status changes, and ophthalmoplegia.

Neuromuscular junction disorders such as botulism and myasthenia gravis present with ophthalmoplegia. In the former, there is a classic rapid progression from the cranial muscles to the limbs leading to respiratory failure. The presence of additional autonomic features should also alert one to this diagnosis. Myasthenia gravis can be differentiated by the absence of ataxia, areflexia, or drowsiness coupled with muscle fatigability on examination.

Brainstem encephalitis associated with glial or neuronal surface antibodies including NMDA receptor antibodies should be included in a differential diagnosis of anti-GQ1b antibody-positive Bickerstaff brainstem encephalitis (13). It is of interest that one of the three original cases described by Bickerstaff and Cloake in 1951, a young woman who developed seizures, eye movement disorders, and acute psychosis while awaiting ovarian cystectomy, had features that may be more consistent with anti-NMDA receptor encephalitis (32).

The differential diagnosis also includes other inflammatory brainstem lesions such as neuro-Behçet disease, neurosarcoidosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), CNS vasculitis, as well as infiltrative disorders such as primary brainstem glioma or CNS lymphoma.

Miller Fisher syndrome or cranial neuropathies can occur as early neurologic manifestations of COVID-19 disease caused by severe acute respiratory coronavirus 2 (SARS-Cov-2) infection without detection of anti-GQ1b antibodies (08; 18). It was also reported that Bickerstaff brainstem encephalitis can develop as a neurologic spectrum of COVID-19 disease (25), but no GQ1b antibodies were detected. It is emphasized that COVID-19 can trigger not only Guillain-Barré syndrome but also other autoimmune neurologic diseases (07). Because GQ1b antibodies have not been identified, a novel antigen might be involved (18); however, overall GQ1b positivity after COVID-19 infection was found to be only 45% (36). GQ1b antibody-positive Miller Fisher syndrome following COVID-19 vaccination has also been reported (35). A review on nine cases of Miller Fisher syndrome following COVID-19 vaccination emphasized that unlike Miller Fisher syndrome following COVID-19 infection, patients with Miller Fisher syndrome following COVID-19 vaccination frequently presented with GQ1b antibody positivity (44% or four out of nine), and Miller Fisher syndrome following COVID-19 vaccination may have a pathophysiology different from Miller Fisher syndrome following COVID-19 infection (19). A systematic literature review found that Miller Fisher syndrome presents on average 7 days after COVID-19 infection and 11 days after COVID-19 vaccination (36).

Case reports also suggest that Miller Fisher syndrome may develop in association with immunotherapy or cancer therapy, including treatment with ipilimumab and nivolumab (31), cemiplimab (11), or the anti-TNF alfa monoclonal antibody, infliximab (53); however, no anti-GQ1b antibodies were detected in these cases. A case of Bickerstaff brainstem encephalitis that developed after autologous stem cell transplant has also been reported (30).

Diagnostic workup

The diagnostic workup should not only look to support the diagnosis of the anti-GQ1b antibody syndrome, but, when appropriate, should address the differential diagnoses discussed above. Patients who present with features suggestive of a central cause of ataxia and drowsiness with ophthalmoplegia will require brain imaging, preferably MRI, to look for evidence of a vascular, infiltrative, or demyelinating disorder. It should be noted that the MRI can be abnormal in only a third of patients with Bickerstaff brainstem encephalitis and 1% of patients with Miller Fisher syndrome, showing increased T2/FLAIR signal in the brainstem, thalamus, cerebellum, cerebrum, or cranial nerves (37; 17; 08). CSF analysis can be normal in Miller Fisher syndrome and its incomplete variants, particularly in the first week of illness, but can also show CSF albuminocytological dissociation. In comparison, the CSF albuminocytological dissociation is less frequent in Bickerstaff brainstem encephalitis (between 35% to 46%) due to a higher frequency of CSF pleocytosis (between 32% to 37%) (37; 17). Electrophysiology in anti-GQ1b antibody syndrome can be normal or show a sensory axonal pattern of neuropathy. The frequency of reduced sensory amplitudes is higher in the median and ulnar nerves compared with the sural nerve (24). In a study, sensory abnormalities were frequently detected in patients, occurring in 94% of patients (45), whereas another group found that an abnormal H-reflex was the most common finding in their patient cohort (44). There have been a handful of case reports of abnormal single fiber electromyography in facial muscles of patients with Miller Fisher (24). Electroencephalogram can show slow waves in both Bickerstaff brainstem encephalitis and Miller Fisher syndrome, but it is not likely to be helpful in discriminating them from other encephalopathies.

The most important test that will distinguish this syndrome from other possible diagnoses, as stated above, in the right clinical setting, is the presence of GQ1b IgG antibodies, which are highly specific for any of the disease phenotypes. A case of GQ1b antibody-positive rhombencephalitis caused by Listeria monocytogenes has been reported; however, it remains unknown whether Listeria infection triggered an autoimmune response (58).

Following the identification of IgG autoantibodies against GQ1b in patients with Miller Fisher syndrome, the authors proposed these GQ1b antibodies as a diagnostic marker of Miller Fisher syndrome (05). Due to the differences in methods and cutoff values, serological results differ somewhat among representative laboratories; however, GQ1b antibodies occur in 83% to 100% of patients with Miller Fisher syndrome. The discovery of the GQ1b IgG antibodies in Bickerstaff brainstem encephalitis supported a common autoimmune mechanism in both Bickerstaff brainstem encephalitis and Miller Fisher syndrome (56). In a further study that investigated the role of antibodies against complexes of GQ1b and GT1a, the presence of complex-enhanced or complex-attenuated GQ1b or GT1a antibodies resulted in different binding affinities to the single ganglioside (GQ1b or GT1a), leading to a range of neurologic features. In another study utilizing the glycoarray methodology, antibodies to antigens containing GQ1b were detected in 73% of patients with Guillain-Barré syndrome and ophthalmoplegia, 87% of patients with Miller Fisher syndrome, and 74% of patients with Bickerstaff brainstem encephalitis, whereas GD1b-related antibodies were identified in 49% of patients with Guillain-Barré syndrome and ophthalmoplegia, 29.7% of patients with Miller Fisher syndrome, and 11% of patients with Bickerstaff brainstem encephalitis (51). The authors also found that patients with Guillain-Barré syndrome with ophthalmoplegia who were seropositive for both antibodies had a higher probability of requiring artificial ventilation than patients without the antibodies.

A 10-year retrospective study of 1342 patients evaluated for anti-ganglioside antibodies using commercially available line blots, in both serum and CSF, found that serum IgG blots associated with Miller Fisher syndrome were GM1, GD1a, GT1a, and GQ1b (12). There was cross-responsiveness in 39.6% of all positive serum anti-ganglioside antibody assays.

A large study of patients with Bickerstaff brainstem encephalitis and Miller Fisher syndrome demonstrated that both conditions had many similarities (17). The peripheral nerves were abnormal (most frequently with an absence of the soleus H reflex) in three of four patients with Bickerstaff brainstem encephalitis and 74% of 28 patients with Miller Fisher syndrome. Body sway analyses showed abnormalities within the proprioceptive afferent system in 67% of three patients with Bickerstaff brainstem encephalitis and 72% of 18 of those with Miller Fisher syndrome. In contrast, brain MRI and EEG recordings were abnormal in patients with Bickerstaff brainstem encephalitis (11% and 57%, respectively), as well as some patients with Miller Fisher syndrome (1% and 25%, respectively), suggesting central components can occasionally be affected in both Bickerstaff brainstem encephalitis and Miller Fisher syndrome. GQ1b antibodies were present in 83% of patients with Miller Fisher syndrome (n=466) and 68% of those with Bickerstaff brainstem encephalitis (n= 53). The same study also described patients who did not fulfill the criteria of either Bickerstaff brainstem encephalitis or Miller Fisher syndrome but had GQ1b antibodies. This group of patients was seen to have less extensive clinical features and could represent a forme fruste of either Bickerstaff brainstem encephalitis or Miller Fisher syndrome. These cases did share similar clinical and serological profiles, including the presence of antecedent infections. Referring to such cases as part of the GQ1b antibody syndrome would allow clinicians to classify the syndrome accordingly.

It is important to mention that testing for serum anti-ganglioside antibodies outside of defined clinical phenotypes is not indicated. Specifically, commercially available anti-ganglioside antibody testing is not recommended in typical Guillain-Barré syndrome and CIDP. CSF anti-ganglioside antibody testing does not offer any additional information.

Management

• To date, there are no well-designed, randomized controlled trials of IVIG or plasmapheresis in Miller Fisher syndrome.

There have been no randomized clinical trials of treatment in anti-GQ1b antibody syndrome, including Miller Fisher syndrome or Bickerstaff brainstem encephalitis specifically. The decision to treat is supported by pathogenesis and should depend on the level of disability experienced by patients. Both IVIg and plasma exchange have been used. Although IVIg slightly hastened recovery in Miller Fisher syndrome, the final outcome remained unchanged (33). Bickerstaff brainstem encephalitis also generally has a good prognosis; however, reports of mortality would justify treatment with either IVIg or plasma exchange. In cases where there are also clinical features resembling Guillain-Barré syndrome, treatment with either plasma exchange or IVIg is recommended as randomized controlled trials have established the efficacy of both treatments in Guillain-Barré syndrome (15). The role of steroids in Bickerstaff brainstem encephalitis is less clear, although there have been reports of clinical improvement with steroid administration. In Guillain-Barré syndrome, steroids administered on their own were associated with clinical deterioration when compared to no treatment (15).

Along with immunotherapy, supportive treatment such as ventilatory support, tube feeding in patients with swallowing difficulties, prophylaxis against thromboembolic events in patients not able to ambulate, and early rehabilitation are also important.

Outcomes

In Miller Fisher syndrome, patients tend to make a spontaneous recovery. Improvement in ataxia is reported to occur 3 to 41 days after onset, followed closely by improvement in ophthalmoplegia (between 3 and 46 days) (34). The median periods of complete resolution take 32 days in ataxia and 88 days in ophthalmoplegia, respectively (34).

In 13 patients with Miller Fisher syndrome, two out of five (40%) patients treated with intravenous immunoglobulin had residual deficits at six months compared to five out of eight (63%) patients who were left untreated (49).

In Bickerstaff brainstem encephalitis, most patients achieve complete remission by six months, but symptoms of dysesthesia, diplopia, or ataxia may persist in a few patients (37).

References

01: Aranyi Z, Kovacs T, Sipos I , Bereczki D. Miller Fisher syndrome: brief overview and update with a focus on electrophysiolgical findings. Eur J Neurol 2012;19(1):15-20. PMID 21631649
02: Bickerstaff ER. Brain-stem encephalitis; further observations on a grave syndrome with benign prognosis. Br Med J 1957;1(5032):1384-7. PMID 13436795
03: Bickerstaff ER, Cloake PC. Mesencephalitis and rhombencephalitis. Br Med J 1951;2(4723):77-81. PMID 14848512
04: Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Ganglioside composition of the human cranial nerves, with special reference to pathophysiology of Miller Fisher syndrome. Brain Res 1997;745(1-2):32-6. PMID 9037391
05: Chiba A, Kusunoki S, Shimizu T, Kanazawa I. Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol 1992;31(6):677-9. PMID 1514781
06: Cunningham ME, McGonigal R, Meehan GR, et al. Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis. Brain 2016;139(Pt 6):1657-65. PMID 27017187
07: Dalakas MC. Guillain-Barré syndrome: the first documented COVID-19-triggered autoimmune neurologic disease: more to come with myositis in the offing. Neurol Neuroimmunol Neuroinflamm 2020;7(5):e781. PMID 32518172
08: Dinkin M, Gao V, Kahan J, et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology 2020;95(5):221-3. PMID 32358218
09: Emilia-Romagna Study Group on Clinical and Epidemiological Problems in Neurology. Guillain-Barré syndrome variants in Emilia-Romagna, Italy, 1992-3: incidence, clinical features, and prognosis. J Neurol Neurosurg Psychiatry 1998;65(2):218-24. PMID 9703176
10: Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 1956;255(2):57-65. PMID 13334797
11: Ghosh A, Harish Bindiganavile S, Bhat N, Lee AG. A case of Miller Fisher syndrome due to the use of cemiplimab. J Neuroophthalmol 2021;41(3):e343-5. PMID 32868575
12: Giesche N, Böhm-Gonzalez ST, Kleiser B, et al. Antiganglioside antibody frequency in routine clinical care settings. Eur J Neurol 2024;31(7):e16290. PMID 38556758
13: Hacohen Y, Nishimoto Y, Fukami Y, et al. Paediatric brainstem encephalitis associated with glial and neuronal autoantibodies. Dev Med Child Neurol 2016;58(8):836-41. PMID 26918533
14: Houliston RS, Koga M, Li J, et al. A Haemophilus influenzae strain associated with Fisher syndrome expresses a novel disialylated ganglioside mimic. Biochemistry 2007;46(27):8164-71. PMID 17567050
15: Hughes RA, Swan AV, Raphael JC, Annane D, van Koningsveld R, van Doorn PA. Immunotherapy for Guillain-Barré syndrome: a systematic review. Brain 2007;130(Pt 9):2245-57. PMID 17337484
16: Ishii J, Yuki N, Kawamoto M, Yoshimura H, Kusunoki S, Kohara N. Recurrent Guillain-Barré syndrome, Miller Fisher syndrome and Bickerstaff brainstem encephalitis. J Neurol Sci 2016;364:59-64. PMID 27084218
17: Ito M, Kuwabara S, Odaka M, et al. Bickerstaff's brainstem encephalitis and Fisher syndrome form a continuous spectrum: clinical analysis of 581 cases. J Neurol 2008;255(5):674-82. PMID 18274803
18: Kajani S, Kajani R, Huang CW, Tran T, Liu AK. Miller Fisher syndrome in the COVID-19 era - a novel target antigen calls for novel treatment. Cureus 2021;13(1):e12424. PMID 33409112
19: Kim JE, Yoon BA, Kim YH, Kim JK, Bae JS. Miller Fisher syndrome following COVID-19 vaccines: A scoping review. Acta Neurol Scand 2022;146(5):604-9. PMID 35938305
20: Kim SH, Baek SH, Lee SU, Yu S, Kim JS. Optic disc edema as a sole manifestation of anti-GQ1b antibody syndrome. J Neurol 2021;268(6):2263-6. PMID 33715026
21: Koga M, Gilbert M, Li J, Koike S, et al. Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry. Neurology 2005;64(9):1605-11. PMID 15883324
22: Koga M, Kusunoki S, Kaida K, et al. Nationwide survey of patients in Japan with Bickerstaff brainstem encephalitis: epidemiological and clinical characteristics. J Neurol Neurosurg Psychiatry 2012;83(12):1210-5. PMID 22851608
23: Kusunoki S, Willison HJ, Jacobs BC. Antiglycolipid antibodies in Guillain-Barré and Fisher syndromes: discovery, current status and future perspective. J Neurol Neurosurg Psychiatry 2021;92(3):311-8. PMID 33376111
24: Kuwabara S, Sekiguchi Y, Misawa S. Electrophysiology in Fisher syndrome. Clin Neurophysiol 2017;128(1):215-9. PMID 27923188
25: Lantos JE, Strauss SB, Lin E. COVID-19-associated Miller Fisher syndrome: MRI findings. AJNR Am J Neuroradiol 2020;41(7):1184-6. PMID 32467190
26: Lee SU, Baek SH, Kim HJ, Choi JY, Kim BJ, Kim JS. Acute comitant strabismus in anti-GQ1b antibody syndrome. J Neurol 2023;270(1):486-92. PMID 36175671
27: Lee SU, Kim HJ, Choi JY, Choi KD, Kim JI. Expanding clinical spectrum of anti-GQ1b antibody syndrome. a review. JAMA Neurol 2024;81(7):762-70. PMID 38739407
28: Liu JX, Willison HJ, Pedrosa-Domellof F. Immunolocalization of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles. Invest Ophthalmol Vis Sci 2009;50(7):3226-32. PMID 19255160
29: Lyu RK, Tang LM, Cheng SY, Hsu WC, Chen ST. Guillain-Barré syndrome in Taiwan: a clinical study of 167 patients. J Neurol Neurosurg Psychiatry 1997;63(4):494-500. PMID 9343130
30: Malhotra A, Latov N. Relapsing Bickerstaff brainstem encephalitis after autologous stem cell transplant. J Clin Neuromuscul Dis 2020;21(4):225-9. PMID 32453098
31: McNeill CJ, Fehmi J, Gladwin J, Price C. A rare case of Miller Fisher variant of Guillain-Barré Syndrome (GBS) induced by a checkpoint inhibitor. BMJ Case Rep 2019;12(8):e229443. PMID 31413049
32: Merwick A, Dalmau J, Delanty N. Insights into antibody-associated encephalitis--Bickerstaff's 1950's papers revisited. J Neurol Sci 2013;334(1-2):167-8. PMID 23927937
33: Mori M, Kuwabara S, Fukutake T, Hattori T. Intravenous immunoglobulin therapy for Miller Fisher syndrome. Neurology 2007;68(14):1144-6. PMID 17404197
34: Mori M, Kuwabara S, Fukutake T, Yuki N, Hattori T. Clinical features and prognosis of Miller Fisher syndrome. Neurology 2001;56(8):1104-6. PMID 11320188
35: Nanatsue K, Takahashi M, Itaya S, Abe K, Inaba A. A case of Miller Fisher syndrome with delayed onset peripheral facial nerve palsy after COVID-19 vaccination: a case report. BMC Neurol 2022;22(1):309. PMID 35996074
36: Neophytou P, Artemiadis A, Hadjigeorgiou GM, Zis P. Miller Fischer syndrome after COVID-19 infection and vaccine: a systematic review. Acta Neurol Belg 2023;123(5):1693-701. PMID 37468803
37: Odaka M, Yuki N, Yamada M, et al. Bickerstaff's brainstem encephalitis: clinical features of 62 cases and a subgroup associated with Guillain-Barré syndrome. Brain 2003;126(Pt 10):2279-90. PMID 12847079
38: Ono M, Sato H, Shirahashi M, et al. Clinical features of Miller-Fisher syndrome in pregnancy. Case Rep Obstet Gynecol 2015;2015:840680. PMID 26697248
39: Racke MK, Niles JK, Lorenz RA, Kaufman HW. Changes in ganglioside antibody positivity rates during the COVID-19 pandemic. J Neuroimmunol 2022;367:577877. PMID 35490444
40: Rodella U, Negro S, Scorzeto M, et al. Schwann cells are activated by ATP released from neurons in an in vitro cellular model of Miller Fisher syndrome. Dis Model Mech 2017;10(5):597-603. PMID 28067631
41: Rodella U, Scorzeto M, Duregotti E, et al. An animal model of Miller Fisher syndrome: mitochondrial hydrogen peroxide is produced by the autoimmune attack of nerve terminals and activates Schwann cells. Neurobiol Dis 2016;96:95-104. PMID 27597525
42: Ropper AH, Shahani B. Proposed mechanism of ataxia in Fisher’s syndrome. Arch Neurol 1983;40(9):537-8. PMID 6615283
43: See FH, Goh Y, Sia CH, et al. A brain-heart interaction: Bickerstaff's brainstem encephalitis with Takotsubo cardiomyopathy. QJM 2021;114(3):204-5. PMID 32642763
44: Sekiguchi Y, Misawa S, Shibuya K, et al. Patterns of sensory nerve conduction abnormalities in Fisher syndrome: more predominant involvement of group Ia afferents than skin afferents. Clin Neurophysiol 2013;124(7):1465-9. PMID 23474054
45: Shahrizaila N, Goh KJ, Kokubun N, Tan AH, Tan CY, Yuki N. Sensory nerves are frequently involved in the spectrum of Fisher syndrome. Muscle Nerve 2014;49(4):558-63. PMID 23893512
46: Shahrizaila N, Yuki N. Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome. J Neurol Neurosurg Psychiatry 2013;84(5):576-83. PMID 22984203
47: Tan CY, Yuki N, Shahrizaila N. Delayed facial palsy in Miller Fisher syndrome. J Neurol Sci 2015;358(1-2):409-12. PMID 26277343
48: Uncini A, Shahrizaila N, Kuwabara S. Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes. J Neurol Neurosurg Psychiatry 2017;88(3):266-71. PMID 27799296
49: Verboon C, van Berghem H, van Doorn PA, Ruts L, Jacobs BC. Prediction of disease progression in Miller Fisher and overlap syndromes. J Peripher Nerv Syst 2017;22(4):446-50. PMID 29065229
50: Wakerley BR, Uncini A, Yuki N, GBS Classification Group. Guillain-Barré and Miller Fisher syndromes--new diagnostic classification. Nat Rev Neurol 2014;10(9):537-44. PMID 25072194
51: Yoshikawa K, Kuwahara M, Morikawa M, et al. Varied antibody reactivities and clinical relevance in anti-GQ1b antibody-related diseases. Neurol Neuroimmunol Neuroinflamm 2018;5(6):e501. PMID 30246056
52: Yoshikawa K, Kuwahara M, Morikawa M, Kusunoki S. Bickerstaff brainstem encephalitis with or without anti-GQ1b antibody. Neurol Neuroimmunol Neuroinflamm 2020;7(6):e889. PMID 32934014
53: Yu EH, Geraldi-Samara D. Pharyngeal-cervico-brachial/Miller Fisher overlap syndrome with infliximab exposure. J Clin Neuromuscul Dis 2020;21(3):157-8. PMID 32073461
54: Yuki N. Acute paresis of extraocular muscles associated with IgG anti-GQ antibody. Ann Neurol 1996;39:668-72. PMID 8619553
55: Yuki N. Fisher syndrome and Bickerstaff brainstem encephalitis (Fisher-Bickerstaff syndrome). J Neuroimmunol 2009;215(1-2):1-9. PMID 19643503
56: Yuki N, Sato S, Tsuji S, Hozumi I, Miyatake T. An immunologic abnormality common to Bickerstaff's brain stem encephalitis and Fisher's syndrome. J Neurol Sci 1993;118(1):83-7. PMID 8229054
57: Zeiner PS, Brandhofe A, Müller-Eschner M, Steinmetz H, Pfeilschifter W. Area postrema syndrome as frequent feature of Bickerstaff brainstem encephalitis. Ann Clin Transl Neurol 2018;5(12):1534-42. PMID 30564620
58: Zhao Y, Xu C, Tuo H, Liu Y, Wang J. Rhombencephalitis due to Listeria monocytogenes infection with GQ1b antibody positivity and multiple intracranial hemorrhage: a case report and literature review. J Int Med Res 2021;49(4):300060521998568. PMID 33866842

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Alexandru C Barboi MD FACP

Dr. Barboi of Indiana University has no relevant financial relationships to disclose.
See Profile

Editor

Francesc Graus MD PhD

Dr. Graus, Emeritus Professor, Laboratory Clinical and Experimental Neuroimmunology, Institut D’Investigacions Biomédiques August Pi I Sunyer, Hospital Clinic, Spain, has no relevant financial relationships to disclose.
See Profile

Former Authors

Nobuhiro Yuki PhD
Nortina Shahrizaila PhD
Takahiro Iizuka MD

Patient Profile

Age range of presentation: Miller Fisher syndrome: median 44 years (range, 2 to 86 years) (Ito et al 2008)

Bickerstaff brainstem encephalitis: median 40 years (range, 0 to 78 years) (Ito et al 2008)
Sex preponderance: Miller Fisher syndrome

Male>female, 1.5:1 (Ito et al 2008)

Bickerstaff brainstem encephalitis

Male>female, 2.3:1 (Ito et al 2008)
Heredity: None
Population groups selectively affected: Higher frequencies reported in Asian populations
Occupation groups selectively affected: None selectively affected

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Anti-GQ1b antibody syndrome

Differential Diagnosis

Acute disseminated encephalomyelitis
Multiple sclerosis
Neuro-Behçet disease
Neurosarcoidosis
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)
- Myasthenia gravis
- Botulism
- Brainstem tumor (eg, gliomas or lymphoma)
- CNS vasculitis (eg, primary CNS angiitis)
- Brainstem stroke (hemorrhage, infarction)
- Wernicke encephalopathy
- Basal meningitis (eg, Cryptococcal meningitis)
- Anti-NMDA receptor encephalitis
- COVID-19 infection

Also Relevant

Acquired sensory neuronopathies
Acute inflammatory demyelinating polyradiculoneuropathy
Acute motor axonal neuropathy
Guillain-Barre syndrome
Sensory neuropathies associated with anti-GD1b ganglioside antibodies

Clinical Categories

Neuroimmunology

Anti-GQ1b antibody syndrome

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Case 1: Eye movements with facial diplegia.

Case 2: Representative case of recurrent Guillain-Barré syndrome or Miller Fisher syndrome.

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Autoantibodies: mechanism and testing

Multiple sclerosis: treatment of its symptoms

Paraneoplastic syndromes

Anti-IgLON5 disease

Balo concentric sclerosis

Anti-LGI1 encephalitis

Progressive encephalomyelitis with rigidity and myoclonus and glycine receptor antibodies

Giant cell arteritis

This is an article preview.
Start a Free Account
to access the full version.