A case of Miller Fisher syndrome with pharyngeal palsy as an initial symptom]

We report herein a rare case of Miller Fisher syndrome with pharyngeal palsy as an initial symptom. A 68-year-old man admitted to our hospital with pharyngeal palsy two weeks after a respiratory infection. He subsequently developed ataxic gait, paresthesia in the upper limbs and ophthalmoplegia. Double-filtrated-plasmapheresis had been performed four times and all the symptoms subsided within two months. In the acute phase of the disease, the titers of anti-GQ1b and GT1a antibodies were elevated. The titer of anti-GT1a antibody was higher than that of anti-GQ1b antibody. Recently, the activity of serum anti-GT1a antibody has been supposed to be associated with pharyngeal palsy. In the present case, higher titer of anti-GT1a antibody compared with that of anti-GQ1b antibody could possibly cause pharyngeal palsy as an initial symptom of Miller Fisher syndrome.     

Clinical correlates of serum anti-GT1a IgG antibodies

Patients with the pharyngeal-cervical-brachial variant (PCB) of Guillain-Barré syndrome (GBS) have anti-GT1a IgG with or without GQ1b reactivity, whereas those with Fisher syndrome (FS) or Bickerstaff's brainstem encephalitis (BBE) have anti-GQ1b IgG antibodies which cross-react with GT1a. The nosological relationship between these conditions has yet to be established. To investigate the relationships between each manifestation and between clinical features and the coexistence of anti-GQ1b IgG, we reviewed neurological signs present during illnesses of 140 patients who had anti-GT1a IgG. Based on our criteria, FS was diagnosed for 64 (46%) patients, GBS for 22 (16%), BBE for 14 (10%), and PCB for 6 (4%). Overlapping conditions were diagnosed for some patients: FS and GBS (5%), PCB and FS (5%), BBE and GBS (4%), and PCB and BBE (1%). Patients who initially had bulbar palsy developed not only PCB but FS or BBE. The population of anti-GT1a-positive patients frequently had ophthalmoplegia, ataxia, and areflexia, whereas the subpopulation who had anti-GT1a IgG without GQ1b reactivity frequently had preceding diarrhea as well as oropharyngeal, neck, and limb weakness. Patients with anti-GT1a IgG presented a variety of clinical conditions, indicative of a continuous clinical spectrum. A major part of this clinical variation was due to the coexistence of anti-GQ1b IgG. The presence of a common autoantibody (anti-GT1a IgG) and overlapping illnesses suggests that PCB is closely related not only to GBS but to FS and BBE as well.     

Antiganglioside antibody in patients with Guillain-Barré syndrome who show bulbar palsy as an initial symptom

OBJECTIVES: To identify valuable antiganglioside antibodies that support the diagnosis of Guillain-Barré syndrome (GBS) and its variants in patients showing bulbar palsy as an initial symptom. METHODS: Medical records of 602 patients with GBS or its variants were reviewed. Fifteen patients had bulbar palsy as an initial symptom. Serum antibodies against GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, and GQ1b were examined in 13 of them. RESULTS: Serum antiganglioside antibodies were positive in 11 (85%) patients. IgG anti-GT1a (n=8; 62%) and anti-GM1b (n=7; 54%) antibodies were often present, whereas all the patients had low or no anti-GM1 antibody activity. High anti-GD1a and anti-GQ1b IgG antibody titres were also present in some patients, but most had higher IgG antibody titres to GM1b or GT1a. All five patients with high IgG antibody titre to GM1b or GT1a only had had antecedent diarrhoea. Some patients with pharyngeal-cervical-brachial weakness (PCB) had IgG antibody to GT1a which did not cross react with GQ1b. Other patients with PCB had antibody to GT1a which cross reacted with GQ1b or antibody to GM1b, but anti-GM1b and anti-GT1a antibodies were not associated with the presence of bulbar palsy. All the patients who had no IgG antiganglioside antibodies recovered completely. CONCLUSIONS: Measurement of serum IgG anti-GT1a and anti-GM1b antibodies gives helpful support for the diagnosis of GBS and its variants when there is early involvement of the oropharyngeal function independently of other neurological findings which appear as the illness progresses.     

Acute ophthalmoplegia with pupillary areflexia associated with anti-GQ1b antibody.

Raised anti-GQ1b antibody is associated with Miller Fisher syndrome, Guillain-Barre syndrome (GBS) with ophthalmoplegia, Bickerstaff's brain stem encephalitis, acute ophthalmoparesis without ataxia and ataxic GBS without opthalmoplegia. We report a rare case of acute ophthalmoplegia associated with anti-GQ1b antibody that also had pupillary areflexia. A 35-year-old Chinese lady presented with external ophthalmoplegia, pupillary areflexia and no other abnormalities of cranial nerves, muscle tone, deep tendon reflexes, limb power or cerebellar dysfunction. Anti-GQ1b IgG antibody titre was significantly elevated, while neuroimaging of brain and orbital structures, nerve conduction study and cerebral spinal fluid examination were normal. Pupillary areflexia should be recognized as another feature that may be present in conditions associated with raised anti-GQ1b antibody.     

Ophthalmoplegic Guillain-Barré syndrome: An independent entity or a transitional spectrum?

Ophthalmoplegia can occur in both Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) with typical limb involvement. However, ophthalmoplegic GBS (OGBS) has been poorly defined. We aimed to characterize OGBS and clarify the pathophysiological implications across the overall GBS spectrum. Twenty GBS and seven MFS patients from three university based teaching hospitals in Korea were enrolled and analyzed. Six GBS patients who were classified as OGBS commonly also had facial diplegia (50%) and bulbar palsy (50%), while only a small portion of non-ophthalmoplegic GBS (NOGBS) patients had facial diplegia (21%). None of the patients had bulbar palsy in the NOGBS or MFS groups. The most frequent anti-ganglioside antibody in OGBS was the IgG anti-GT1a antibody (50%). The IgG anti-GM1 antibody was found mainly in NOGBS (57%) with high concordance with the pure motor type classification on electrophysiology. IgG anti-GQ1b antibody was positive uniquely in MFS (100%), although some patients were also positive for anti-GT1a antibody (71%). OGBS had distinct clinical features, including bulbar palsy, as well as ophthalmoplegia and limb weakness for both GBS and MFS. Relevant immunological factors were anti-GT1a antibody. Whether OGBS is an independent entity or a transitional spectrum remains to be established and further study will be needed.     

A case of atypical Guillain-Barré syndrome exclusively showing multiple cranial nerve palsy with an elevation of anti-GQ1b and anti-GT1a IgG antibodies]

This is a case report of atypical Guillain-Barré syndrome (GBS). A 42-year-old woman displayed pharyngeal paralysis after a mild upper respiratory infection, subsequently having developed ophthalmoplegia, facial diplegia and accessory nerve palsy within about ten days. She had neither weakness nor abnormal tendon reflexes in the extremities. During the acute phase of the disease we found significant elevation of anti-GQ1b and anti-GT1a IgG antibodies in the serum, and immunoadsorption therapy had a remarkable effect on the symptoms. Although our case was extremely atypical of GBS in terms of exclusively showing multiple cranial nerve palsy and lacking areflexia, the elevation of anti-glycolipid antibodies during the acute phase suggests that this case shares pathogenesis with GBS.     

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.     

A case with upper limb dominant Guillain-Barré syndrome and serum IgG anti-GT1a antibodies: sparing oropharyngeal palsy]

We report a 78-year-old man with Guillain-Barré syndrome (GBS) who showed upper limb dominant muscle weakness following an upper respiratory infection. He had no weakness in extraocular, oropharyngeal and neck muscles. Tendon reflexes were absent in his upper limbs. Electrophysiological studies suggested demyelination of motor nerves in his upper and lower extremities. He had serum IgG antibodies to GM1 and GT1a but not to GQ1b. Anti-GT1a antibodies did not cross-react to GM1 by means of the absorption test. Titers of the antibodies decreased after recovering from muscle weakness of upper limbs. Since the presence of serum antibodies to GT1a but not to GQ1b were reported in patients with pharyngeal-cervical-brachial weakness of Guillain-Barré syndrome, it has been suggested that anti-GT1a antibodies play a role in acute oropharyngeal neuropathy. This is the first report of a patient with GBS lacking oropharyngeal palsy who had serum IgG antibodies to GT1a but not to GQ1b. Our case suggests that anti-GT1a antibodies are related not only with acute oropharyngeal neuropathy but also with upper limb dominant motor neuropathy.     

A case of Fisher syndrome showing pharyngeal-cervical-brachial weakness with an elevation of anti-GQ 1 b and anti-GT 1 a antibodies]

A 15-year-old boy developed ataxic gait, diplopia and hoarseness. Within 3 days after the onset, he had additional symptoms of dysphagia and dysarthria. He was admitted to our hospital 7 days after the onset of the disease. On admission, he had total ophthalmoplegia, ataxia, areflexia, facial diplegia, bulbar palsy and weakness of the neck and upper arms. Serum anti-GQ 1 b and anti-GT 1 a antibodies were significantly elevated. A diagnosis of Fisher syndrome associated with pharyngeal-cervical-brachial weakness was made. He was placed on a high dose of intravenous immunoglobins (12.5 g/day x 2 days) and had steroid pulse therapy (methylprednisolone 1 g x 3 days), which resulted in an almost complete recovery. There have been no reports of Fisher syndrome associated with brachio-pharyngeal-palsy. As in the case of the pharyngeal-cervical-brachial variant of Guillain Barré syndrome, anti-GT 1 a antibodies may be associated with Fisher syndrome with pharyngeal-cervical-brachial weakness.     

Ataxic Guillain-Barré syndrome with delayed facial diplegia]

We described a patient with ataxic Guillain-Barré syndrome who subsequently developed facial diplegia. A 38-year-old man developed ataxia, distal limb paresthesias, mild dysphagia, urinary retention and orthostatic hypotension a week after an episode of laryngitis. He had high titers of serum anti-GQ1b, anti-GD1b, anti-GM1b, anti-GT1a, and anti-GD1a IgG antibodies during the acute phase. Although the initial symptoms markedly improved by intravenous immunoglobulin therapy, asymmetric facial diplegia subsequently occurred and remained longer than ataxia. Similar course of facial nerve palsy has been reported in patients with Fisher syndrome. Common pathophysiological mechanism may function in the development of delayed facial diplegia in Fisher syndrome and ataxic Guillain-Barre syndrome.     

A case of acute oropharyngeal palsy with nasal voice as main symptom]

We report a patient with acute oropharyngeal palsy following enteritis. A 19-year-old woman developed increasing nasal voice over a few days. Neurological examination on day 7 of her course showed paretic dysarthria and mild weakness of neck flexion and quadriceps femoris muscle (Medical Research Council grade, 4+). Her palatal movement was diminished, whereas both palatal and pharyngeal reflex was normal. She could swallow water, although she had a slight amount of liquid reflux to her nose on swallowing. High titers of serum anti-Campylobacter jejuni, anti-GQ1b and anti-GT1a IgG antibodies were detected. Her symptoms improved gradually without any treatment, and disappeared by 40 days from neurological onset. Nasal voice with slight swallowing impairment as initial symptom has been rarely reported, but can occur in acute oropharyngeal palsy. Therefore, neurologists should take into account the possibility of Guillain-Barré syndrome and the regional variants in patients who show nasal voice during the initial stage.     

Anti-GQ1b IgG-negative case of overlapping Fisher's and Gullain-Barré syndromes after Campylobacter jejuni (PEN 19) enteritis]

We described a 70-year-old woman with overlapping Fisher's syndrome (FS) and Guillain-Barré syndrome (GBS), from whom Campylobacter jejuni had been isolated. In typical FS as well as GBS with ophthalmoplegia and acute ophthalmoparesis without ataxia, serum anti-GQ1b IgG antibody often is detected and ophthalmoplegia is characterized by the predominant abducens palsy. This patient, however, showed marked oculomotor nerve disturbance. Serum anti-GQ1b IgG antibody was negative and IgG antibodies against GM1, GM1b, and GD1a were strongly positive. Although FS and overlap of FS/GBS have been reported to be associated with PEN2 of C. jejuni, the isolate from our case belonged to PEN 19. C. jejuni serotype may be associated with clinical manifestations and anti-ganglioside antibody species.     

Anti-GQ1b IgG antibody is associated with ataxia as well as ophthalmoplegia.

Close association between the increase in anti-GQ1b immunoglobulin G (IgG) antibody and ophthalmoplegia in Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) has been reported. We investigated whether anti-GQ1b IgG antibody also is associated with ataxia, another of the MFS triad. Of 149 patients who had anti-GQ1b IgG antibody without profound weakness, 144 showed ophthalmoplegia (120 showed both ophthalmoplegia and ataxia; 24, ophthalmoplegia without ataxia). In contrast, five showed ataxia without ophthalmoplegia. Some large neurons of the dorsal root ganglia were immunostained with anti-GQ1b monoclonal antibody. Anti-GQ1b IgG antibody may thus be associated with ataxia as well as ophthalmoplegia. Ataxia may be due to its binding to a subset of primary sensory neurons.     

Chronic ophthalmoplegia with anti-GQ1b antibody

Anti-GQ1b antibodies are typically found in patients with the Miller Fisher syndrome, all of whom will have, by definition, acute ophthalmoplegia. The authors describe three patients with chronic ophthalmoplegia in the presence of persistently high titers of immunoglobulin G anti-GQ1b antibody detected in an ELISA, one of whom improved with immunotherapy. Anti-GQ1b antibodies may be associated with some cases of chronic ophthalmoplegia of unknown cause.     

Acute isolated bulbar palsy with anti-GT1a IgG antibody subsequent to Campylobacter jejuni enteritis

We describe a patient with acute isolated bulbar palsy following enteritis. A 29-year-old man developed dysphagia and nasal voice without limb weakness, ataxia, or areflexia. High titres of serum anti-GT1a and anti-Campylobacter jejuni IgG antibodies were detected. He was treated with plasmapheresis, resulting in rapid clinical improvement. This case suggests that an acute isolated bulbar palsy may be caused by a pathology relating to Guillain-Barré syndrome (GBS), in which anti-GT1a IgG antibody may have a role.     

Anti-GT1a IgG in Guillain-Barré syndrome

OBJECTIVE: To investigate the presence of serum anti-GT1a IgG in Guillain-Barré syndrome (GBS) and its relation to clinical manifestations. BACKGROUND: Several patients with GBS and bulbar palsy have been reported to have serum anti-GT1a IgG. Most, however, also have anti-GQ1b IgG. A previous study failed to detect GT1a in human cranial nerves, but GQ1b was abundant in human ocular motor nerves. Whether anti-GT1a IgG itself determines the clinical manifestations is not yet clear. METHODS: The association of clinical manifestations with the presence of anti-GT1a IgG and with its cross reactivity was investigated. An immunochemical study was performed to determine whether GT1a is present in human cranial nerves. RESULTS: Anti-GT1a and anti-GQ1b IgG were positive in 10% and 9% respectively of 220 consecutive patients with GBS. Patients with anti-GT1a IgG often had cranial nerve palsy (ophthalmoparesis, 57%; facial palsy, 57%; bulbar palsy, 70%), and 39% needed artificial ventilation. These features were also seen in patients with anti-GQ1b IgG. There was no significant difference between the two groups with respect to the frequency of clinical findings. An enzyme-linked immunosorbent assay showed that anti-GT1a IgG cross reacted with GQ1b in 75% of the patients, GD1a in 30%, GM1 in 20%, and GD1b in 20%. All five patients who carried anti-GT1a IgG that did not cross react with GQ1b had bulbar palsy, neck weakness, absence of sensory disturbance, and positive Campylobacter jejuni serology. Thin-layer chromatography with immunostaining showed that GT1a is present in human oculomotor and lower cranial nerves. CONCLUSIONS: These findings provide further evidence that anti-GT1a IgG itself can determine clinical manifestations. The distinctive clinical features of patients with anti-GT1a IgG without anti-GQ1b activity distinguish a specific subgroup within GBS.     

Internal ophthalmoplegia in acute oropharyngeal palsy with anti-GQ1b and anti-GT1a IgG antibodies]

A patient with acute oropharyngeal palsy associated with internal ophthalmoplegia was reported. A 13-year-old boy had fever and diarrhea for two days. Ten days after resolution of these symptoms, he noticed difficulty in speaking (day 1). Neurological findings on day 4 included bilateral mydriasis, right abducens nerve palsy, nasal voice with absent pharyngeal reflex. Although superficial sensation was preserved, vibratory sensation was reduced in distal limbs. Tendon reflexes were generally absent. Neither ataxia nor dysautonomia was seen. Serum anti-glycolipid antibody assay on day 4 disclosed elevated IgG antibodies to GQ1b and GT1a. His cerebrospinal fluid on day 21 contained 6 mononuclear cells/microl with 137 mg/dl of total protein. Nerve conduction study on day 5 showed minimal sensory nerve involvement. Quantitative sudomotor axon reflex test was normal in the lower extremities. Low dose pilocarpine eyedrops dilated his pupils. Although mild cerebellar-like ataxia appeared on day 5, intravenous immunoglobulin (0.4 g/kg/day for four days) rapidly improved his neurological abnormalities. IgG anti-GQ1b antibody might contribute not only oropharyngeal weakness but also internal ophthalmoplegia in this patient.     

A case of anti-GQ1b-positive atypical Fisher syndrome with internal ophthalmoplegia but without external ophthalmoplegia]

We report a 21-year-old man who developed an atypical form of Fisher syndrome. One week after having a common cold, he was admitted to our hospital because of a gait disturbance. Neurological examination revealed a somnolent state, cerebellar ataxia, areflexia, limb muscle weakness, and numbness in a glove and stocking like distribution. The patient had internal ophthalmoplegia but did not have external ophthalmoplegia. Brain MRI showed no abnormality in the orbital and the pretegmental brain regions. The protein level in the cerebrospinal fluid was 57 mg/dl and the cell count was 5 mononuclear cells/mm3. His serum titer of anti-GQ1b IgG antibody was markedly elevated. There have been only two previous reports of isolated internal ophthalmoplegia with elevated anti-GQ1b antibody. The present case suggests that anti-GQ1b antibody play an important role in the pathogenesis of patients who present with internal ophthalmoplegia but without external ophthalmoplegia.     

Bickerstaff's brainstem encephalitis associated with IgM antibodies to GM1b and GalNAc-GD1a

This is the first report of a case of Bickerstaff's brainstem encephalitis (BBE) associated with IgM antibodies to GM1b and GalNAc-GD1a. Subsequent to Campylobacter jejuni enteritis, the patient rapidly developed consciousness disturbance and hyperreflexia in addition to external ophthalmoplegia and cerebellar-like ataxia. EEG showed transient 7 Hz monorhythmic theta activities, predominantly in the front-central area. He received high doses of immunoglobulin intravenously and had completely recovered 3 months later. High anti-GM1b and anti-GalNAc-GD1a IgM antibody titers present during the acute phase decreased with his clinical improvement. An absorption study showed the anti-GM1b and anti-GalNAc-GD1a IgM antibodies to be cross-reactive. Anti-GM1b and anti-GalNAc-GD1a antibodies have been detected in some patients who developed Guillain-Barré syndrome after C. jejuni enteritis, whereas the anti-GQ1b IgG antibody is associated with BBE. Infection by C. jejuni bearing a GM1b-like or GalNAc-GD1a-like lipooligosaccharide may trigger the production of anti-GalNAc-GD1a and anti-GM1b IgM antibodies. It is not clear why our patient developed BBE rather than Guillain-Barré syndrome. These antibodies may, however, prove useful serological markers for identifying BBE patients who do not have the anti-GQ1b IgG antibody.     

Miller Fisher syndrome with negative anti-GQ1b immunoglobulin G antibodies

Miller Fisher syndrome is characterized by a triad of ataxia, ophthalmoplegia, and reduced or absent tendon reflexes, with minimal if any limb weakness. Anti-GQ1b immunoglobulin G antibodies are present in high titers in most patients. Presented is a two-year-old female with Miller Fisher syndrome whose blood serum was negative for anti-GQ1b immunoglobulin G antibodies.