Recurrent Miller Fisher Syndrome in Children

BackgroundMiller Fisher syndrome is usually a monophasic disorder. Recurrent Miller Fisher syndrome is extremely rare, and all patients with recurrences have been adults. Although the optimal treatment for Miller Fisher syndrome has yet to be established, the typical therapy includes intravenous immunoglobulin or plasma exchange. The efficacy of steroids is still debated.PatientsWe describe two children with recurrent Miller Fisher syndrome. Episodes occurred at the age of 11.5 and 13 years in patient 1 and at the age of 8 and 13 years in patient 2.ResultsClinical patterns of the first and recurrent episodes of Miller Fisher syndrome were overlapping. In both patients, steroids were effective in controlling clinical deterioration of Miller Fisher syndrome recurrences.ConclusionsRecurrent Miller Fisher syndrome is a rare disorder that may occur in children. Our observations and a review of the literature suggest that there may be a small group of patients in whom steroids may be a therapeutic option when intravenous immunoglobulin fails to control clinical symptoms.     

Atypical Miller Fisher syndrome with GQ1b antibodies

An atypical case of Miller Fisher syndrome is described in a patient with ophthalmoplegia and mild ataxia but no areflexia. High titres of acute phase antibodies to gangliosides asialo-GM1 and GQ1b were detected. Asialo-GM1 antibodies have not been previously reported in association with Miller Fisher syndrome. Considerable clinical recovery occurred in association with reduction in the ganglioside antibody titres. Ganglioside antibody assays may be helpful in the diagnosis of atypical cases of Miller Fisher syndrome. Detailed clinical, radiological and laboratory evaluation of suspected cases is warranted to improve our understanding of Miller Fisher syndrome. Such studies and the correlation with ganglioside antibody titres will also provide insights into the relationship between the classical and atypical cases of Miller Fisher syndrome, Guillain-Barré syndrome and Bickerstaff's brain stem encephalitis.     

Anti-GQ1b-Negative Miller Fisher Syndrome After Campylobacter jejuni Enteritis

Miller Fisher syndrome is a clinical variant of Guillain-Barré syndrome, characterized by acute-onset ophthalmoplegia, ataxia, and areflexia. It results from an immune response to a cross-reactive antigen between GQ1b ganglioside in human neurons and lipo-oligosaccharides of certain bacteria, e.g., Campylobacter jejuni. Anti-GQ1b antibody is a powerful diagnostic marker for Miller Fisher syndrome. However, only a small number of anti-GQ1b-negative Miller Fisher syndrome cases are documented. A 13-year-old boy demonstrated typical clinical features of Miller Fisher syndrome 1 week after C.?jejuni enteritis, but was anti-GQ1b and anti-GM1b antibody-negative.     

Familial Miller Fisher syndrome

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

Miller Fisher syndrome and Escherichia coli infection: is it a novel association?

Miller Fisher syndrome is characterized by ataxia, ophthalmoplegia, and reduced or absent tendon reflexes. Generally, it is considered an acute postinfectious paralytic illness caused by a wide variety of infections including Campylobacter jejuni. The authors report the case of a 10-year-old girl with Miller Fisher syndrome who had a previous infection of Escherichia coli. If confirmed by other reports, this report could disclose a new association of Miller Fisher syndrome with E coli infection.     

Miller Fisher syndrome associated with Q fever.

A 51 year old woman with pneumonia developed Miller Fisher syndrome. Indirect immunofluorescence tests showed antibodies against Coxiella burnetti. Miller Fisher syndrome associated with Q fever has not been described previously.     

Observations on the lesion site in the Miller Fisher syndrome: presentation of a case including CT and MRI

Debate about the lesion site in the Miller Fisher syndrome is still going on. We studied a patient with features of the Miller Fisher syndrome in whom arguments for both central and peripheral nervous system dysfunction were found.     

Transcranial magnetic stimulation studies in the Miller Fisher syndrome: evidence of corticospinal tract abnormality.

OBJECTIVES: To evaluate serial central motor conduction time in the Miller Fisher syndrome. METHOD: Three patients with classic Miller Fisher syndrome were evaluated clinically. They had serial central motor conduction times measured with transcranial magnetic stimulation and nerve conduction studies. Motor evoked potentials were recorded from the first dorsal interossei and abductor hallucis muscles. RESULTS: All three patients showed reduction in central motor conduction times in tandem with gradual clinical improvement at each review. CONCLUSIONS: There is electrophysiological evidence of a central reversible corticospinal tract conduction abnormality in the Miller Fisher syndrome.     

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 related to Orientia tsutsugamushi infection

Miller Fisher syndrome is typically associated with a preceding infection, especially with Campylobacter jejuni. We describe a patient with Miller Fisher syndrome following Orientia tsutsugamushi infection, which to our knowledge has not been previously reported.     

Miller Fisher综合征14例报道

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

Three patients with ophthalmoplegia associated with Campylobacter jejuni

Cranial polyneuropathy is idiopathic in most patients. Idiopathic cranial polyneuropathy is an acute postinfectious syndrome, along with Guillain-Barré syndrome and Miller Fisher syndrome, in which the common preceding pathogen is Campylobacter jejuni. Serum anti-GQ1b antibodies are elevated in Miller Fisher syndrome and Guillain-Barré syndrome with ophthalmoplegia. Three patients with idiopathic cranial polyneuropathy with predominant ocular involvement are presented. C. jejuni isolated from stool specimens belonged to Penner serotypes O:4, O:23, and O:33. Serum anti-GQ1b antibodies were elevated in all patients but demonstrated rapid reduction concomitant with clinical recovery. All patients recovered completely. Because both preceding C. jejuni infection and elevated anti-GQ1b antibodies decreasing with time were seen in all patients, the pathogenesis of idiopathic cranial polyneuropathy with ophthalmoplegia may be similar to that of Miller Fisher syndrome.     

Development of facial palsy during immunoadsorption plasmapheresis in Miller Fisher syndrome: a clinical report of two cases

Immunoadsorption plasmapheresis (IAP) using a tryptophan linkedgel column has been shown to effectively remove serum IgG anti-GQ1bantibody which may contribute to the pathogenesis of Miller Fishersyndrome. Two patients are reported on with Miller Fisher syndrome, whodeveloped bilateral facial palsy during IAP using a tryptophan column,while ophthalmoplegia, ataxia, and, areflexia were improving. In thesepatients, the titre of anti-GQ1b antibodies was reduced. The IAP usinga tryptophan column has a beneficial effect on Miller Fisher syndromebut may not inhibit the development of facial palsy. The mechanism ofsuch a dissociated effect of IAP on Miller Fisher syndrome is discussed.

     

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.     

Guillain-Barré syndrome variants in Emilia-Romagna,Italy, 1992-3: incidence,clinical features,and prognosis

OBJECTIVES—To estimate the incidence rate of Guillain-Barré syndrome variants in an unselected population and to describe their clinical features and prognosis.
METHODS—A two year prospective multicentre study on the incidence and prognosis of Guillain-Barré syndrome was performed in Emilia-Romagna, northern Italy (3 909 512 inhabitants). A surveillance system was instituted within the study area, which comprised all the neurological departments, private and public general hospitals, and practising neurologists. The international classification of diseases (ICD) codes 357.XX (any peripheral neuropathy) of hospital discharges were also reviewed.
RESULTS—Data were separately analysed for Miller Fisher syndrome and other Guillain-Barré syndrome variants. During the study period 18 patients with Guillain-Barré syndrome variants including seven with Miller Fisher syndrome were recruited; the incidence rates were 0.14/100 000/year (95% confidence interval (95% CI) 0.07-0.25) for Guillain-Barré syndrome variants (excluding Miller Fisher syndrome) and 0.09/100 000/year (95% CI 0.04-0.18) for Miller Fisher syndrome. Guillain-Barré syndrome variants alone (excluding Miller Fisher syndrome) accounted for 10.5% of total cases. Death and relapses were not found. Details of clinical, electrophysiological, and CSF findings of Guillain-Barré syndrome variants are provided.
CONCLUSIONS—Guillain-Barré syndrome variants other than Miller Fisher syndrome, as obtained through a population based study, account for about 10% of total cases of Guillain-Barré syndrome and, as a whole, have a good prognosis. Their clinical features are heterogeneous; bifacial weakness (associated with other signs, mainly sensory disturbances) represents the most frequent finding.

     

Benign intracranial hypertension: atypical presentation of Miller Fisher syndrome?

Acute ocular paresis, nausea, vomiting, and headaches associated with high intracranial pressure without obvious intracranial pathology are typical features of benign intracranial hypertension. We describe two young children whose presentation, initially suggestive of idiopathic or benign intracranial hypertension, evolved to comprise ophthalmoplegia, ataxia, and areflexia. This triad characterizes Miller Fisher syndrome, a clinical variant of Guillain-Barré syndrome that occurs rarely among children. In both patients, this diagnosis was supported by the clinical course and neurophysiologic findings. Plasma serology was positive for Campylobacter jejuni and anti-GQ1b antibodies in one patient and for antimyelin antibodies in the other. This report of two children with Miller Fisher syndrome presenting with intracranial hypertension adds to the findings for a similar patient treated previously, which raises the question concerning the possible role or contribution of benign intracranial hypertension in Miller Fisher syndrome.     

Pre‐ and postsynaptic blockade of neuromuscular transmission by Miller–Fisher syndrome IgG at mouse motor nerve terminals

Miller–Fisher syndrome, a variant of an acute inflammatory neuropathy is often associated with serum antibodies to the ganglioside GQ1b, but the pathogenic role of these antibodies and other serum factors is unclear. We here investigated the effect of highly purified immunoglobulin G (IgG) from patients with typical Miller–Fisher syndrome, recording quantal endplate currents by means of a perfused macro-patch-clamp electrode on hemidiaphragms of adult mice. The GQ1b-positive and the GQ1b-negative Miller–Fisher IgG as well as its monovalent Fab-fragments depressed evoked quantal release in a fast and fully reversible, concentration and voltage dependent manner. The time-course of quantal release was changed with the late releases becoming more frequent. The extent of depression of release followed a Michaelis–Menten kinetic and depended on the extracellular calcium concentration. In addition the amplitude of quanta was reduced postsynaptically. IgG and sera from healthy subjects had no effect. Our results indicate that in Miller–Fisher syndrome, IgG antibodies to an undetermined antigen depress the release process, most likely by interfering with the presynaptic Ca²⁺ inflow or by interacting with proteins of the exocytotic apparatus, and prevent the activation of postsynaptic channels. Antibodies thus seem to be one pathogenic factor for muscle weakness in Miller–Fisher syndrome and our findings may explain why muscle strength recovers rapidly after therapeutical plasmapheresis.     

Anti-GQ1b ganglioside antibody in peripheral nervous system disorders: pathophysiologic role and clinical relevance

The recent literature about autoimmune peripheral neuropathies has been dominated by the discovery of antibodies to a variety of glycosphingolipids. Gangliosides are important carbohydrate determinants for autoimmune activity, and several studies have suggested that serum antibodies against gangliosides are responsible for some forms of acute and chronic neuropathy syndromes. However, this view is disputable, and despite substantial progress in understanding the potential pathogenic effects of antiganglioside antibodies, many central issues remain unresolved across the whole pathogenic process. Miller Fisher syndrome has been classified as a variant of Guillain-Barré syndrome that comprises the clinical triad of ataxia, areflexia, and ophthalmoplegia. It has been considered the archetypal antiganglioside antibody-mediated human neuropathy because anti-GQ1b ganglioside antibody is detected in most patients with Miller Fisher syndrome, decays rapidly with clinical recovery, and is not found in normal and disease control serum samples. The only other case in which this antibody is found is in patients with related conditions, which might share the same pathogenic mechanism, such as Bickerstaff brainstem encephalitis. The strength of this close serologic-clinical association is such that measurement of anti-GQ1b antibody in suspected cases of Miller Fisher syndrome is a useful diagnostic marker for clinicians. This article reviews the occurrence, the pathophysiologic role, and the clinical background of anti-GQ1b ganglioside antibody in Miller Fisher syndrome and related disorders.     

Proximal conduction abnormality of the facial nerve in Miller Fisher syndrome: a study using transcranial magnetic stimulation.

OBJECTIVE: To investigate facial nerve conduction, including its proximal segment, in Miller Fisher syndrome. METHODS: Three patients underwent facial nerve conduction studies comprising stylomastoid electrical stimulation and transcranial magnetic stimulation at the entrance of the facial canal within the skull and of the cortical representation area. All 3 patients presented with acute bilateral complete ophthalmoplegia, areflexia, mild ataxia and varying other symptoms. One of the patients had bilateral facial palsy; the other two had normal facial innervation. RESULTS: Findings suggestive of demyelination of the proximal segment of the facial nerve were observed in each of the 3 patients with Miller Fisher syndrome. The patient with bilateral facial palsy had absent responses to canalicular stimulation on both sides, while the other two showed increased temporal dispersion and prolonged latency in the proximal nerve segments. CONCLUSIONS: Our findings suggest that the primary pathology of facial nerve lesion in Miller Fisher syndrome is demyelination and that it is localized to the proximal nerve segment. This is in line with the known vulnerability of proximal nerve segments (spinal roots) in other dysimmune demyelinating polyneuropathies. SIGNIFICANCE: Facial nerve conduction study with magnetic stimulation can localize and detect even subclinical facial nerve dysfunction in patients with Miller Fisher syndrome. The technique may contribute to the diagnosis of this disease, where electrophysiologic findings are scanty.