Miller Fischer syndrome after COVID-19 infection and vaccine: a systematic review.

BACKGROUND: COVID-19 (CoranaVirus disease 2019) is an ongoing infectious disease caused by the RNA SARS-CoV-2 virus (Severe Acute Respiratory Syndrome CoronaVirus-2). The virus mainly causes respiratory symptoms, but neurological symptoms have also been reported to be part of the clinical manifestations of the disease. The aim of this study was to systematically review Miller fisher syndrome (MFS) published cases, in the context of COVID-19 infection or vaccination. METHODS: A systematic literature review on Medline was performed. A total of 21 papers were included in the present review. RESULTS: Twenty-two MFS cases (77% males) were identified, 14 related to COVID-19 infection and 8 to vaccination against COVID-19. The median age of the adult patients was 50 years (interquartile range 36-63 years). Sixteen patients (73%) had the classic triad of MFS (ophthalmoplegia, ataxia, areflexia), four (18%) had acute ophthalmoplegia and one other characteristic symptom and two patients (9%) had only one other characteristic symptom, but they tested positive for GQ1b antibodies. Nine (41%) patients had positive GQ1b antibodies and were classified as "definite" MFS. Albuminocytologic dissociation was found in half of the cases. The outcome was favourable in the majority of cases (86%) whereas one patient, despite the initial improvement, died because of a cardiac arrest, after cardiac arrythmia. CONCLUSIONS: MFS after COVID-19 infection/vaccination was found to have the typical epidemiological characteristics of classic MFS; being rare, occurring more often after infection than vaccination, affecting mainly middle-aged males usually within 3 weeks after the event and having an excellent prognosis after treatment with IVIG or even with no treatment at all. We found no evidence that MFS after COVID-19 infection was different from MFS after COVID-19 vaccination, although the former tended to occur earlier.

Nationwide survey of childhood Guillain-Barré syndrome, Fisher syndrome, and Bickerstaff brainstem encephalitis in Japan.

OBJECTIVE: Guillain-Barré syndrome (GBS), Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE) are immune-mediated neuropathies presenting with symptoms such as weakness, ophthalmoplegia, ataxia, and consciousness disturbances. Although the epidemiology of GBS and BBE in patients of all ages has been reported, childhood data have not been well-investigated. We aimed to determine the clinical features, therapeutics, and prognoses of childhood GBS, FS, and BBE in Japan. METHODS: We sent questionnaires to 1068 pediatric neurologists in Japan from 2014 to 2016 to determine the number of children less than 15 years old with GBS, FS, or BBE and their age and sex. We subsequently performed a secondary survey to investigate the clinical features, laboratory data, treatment, and prognosis. RESULTS: Five-hundred thirty-eight pediatric neurology specialists (50.4%) responded to the first survey. The total number of children with GBS, FS, and BBE in Japan from 2014 to 2016 were 87, 10, and 6, respectively. GBS was classified as acute inflammatory demyelinating neuropathy (35.6%), acute motor axonal neuropathy (20.7%), or acute motor-sensory axonal neuropathy (10.3%), with a male-to-female ratio of 1.29:1.0 and a wide distribution of onset ages. The disease severities of GBS, FS, and BBE were variable, but all children could walk within one year. CONCLUSION: The prognoses of childhood GBS, FS, and BBE were generally favorable, as long as the patient was promptly treated with either intravenous immunoglobulin or plasma exchange.

Guillain-Barré syndrome in children - High occurrence of Miller Fisher syndrome in East Asian region.

BACKGROUND: Guillain-Barré syndrome (GBS) is a rare acquired immune-mediated polyneuropathy. Updated population-based data concerning paediatric GBS is needed. METHODS: Paediatric patients aged below 18 years diagnosed with GBS between 2009 and 2018 in all 11 paediatric departments in Hong Kong were identified from the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. The collected data from medical health records were reviewed by paediatric neurologist from each department. Estimated incidence of paediatric GBS was calculated. We also compared our findings with other paediatric GBS studies in Asia. RESULTS: 63 subjects of paediatric GBS were identified, giving an estimated annual incidence of 0.62 per 100,000 population. Half of the subjects had acute inflammatory demyelinating polyneuropathy (AIDP) (n = 31; 49.2%), one quarter had Miller Fisher Syndrome (MFS) (n = 16; 25.4%), one-fifth had axonal types of GBS (n = 12; 19.0%), and four were unclassified. Paediatric subjects with axonal subtypes of GBS compared to the other 2 subtypes, had significantly higher intensive care unit (ICU) admission rates (p = 0.001) and longest length of stay (p = 0.009). With immunomodulating therapy, complete recovery was highest in those with MFS (100%), followed by AIDP (87.1%) and axonal GBS (75%). Our study also confirms a higher MFS rate for paediatric GBS in East Asia region and our study has the highest MFS rate (25.4%). CONCLUSION: Our population-based 10-year paediatric GBS study provides updated evidence on estimated incidence, healthcare burden and motor outcome of each subtype of paediatric GBS and confirmed a higher occurrence of paediatric MFS in East Asia.

Seasonality in the incidence of anti-GQ1b antibody syndrome-A territory-wide study.

AIMS: To investigate any seasonality in the incidence of anti-GQ1b antibody syndrome (AGS). METHODS: We conducted a retrospective observational study in all hospitalized patients in local public hospitals from January 2013 to December 2018. AGS was defined by hospitalized patients with positive serum anti-GQ1b IgG, presumably encompassing Miller-Fisher syndrome, Bickerstaff brainstem encephalitis and Guillain-Barré syndrome (GBS) variants. GBS cases were retrieved from the computerized database by diagnostic label. Campylobacter jejuni infection (CJI) injection was identified by positive stool culture. Monthly incidence rates of AGS, GBS and CJI were calculated. Poisson and negative binomial regression models with long-term time trend were fitted to characterize the seasonal pattern. RESULTS: A total of 237, 572 and 2434 cases of AGS, GBS and CJI were identified, respectively, in a population of 7.3 million. The annual incidence rate of AGS was 0.54 per 100,000 person-years. AGS was demonstrated to have an annual peak in the spring season, from March to April, which was congruent with that of GBS and slightly lagged the annual peak of CJI from February to March (likelihood ratio tests all p < .001 for the seasonal terms). CONCLUSION: The incidence of AGS peaks in springtime, which is congruent with that of GBS and lags around one month after that of CJI. We demonstrated that AGS has a clear seasonality in occurrence.

Classic and overlapping Miller-Fisher syndrome: clinical and electrophysiological features in Mexican adults.

Classic and overlapping Miller-Fisher syndrome (MFS) have divergent clinical courses. Few studies have addressed the electrophysiological evaluation of MFS patients, most of them carried out in Asia. This work describes and compares their clinical and neurophysiological characteristics. From a Guillain-Barré syndrome (GBS) patient cohort, we made a selection of twenty MFS cases. We defined classic and overlapping MFS, as stated by Wakerley et al. (Nat Rev Neurol 10(9):537-544, 2014). We describe and compare clinical, biochemical, and electrodiagnostic parameters between groups. Seventy-five percent were men, mean age was 42.2 ± 13.6 years, and 45% had a Hughes score ≥ 3. MFS/GBS was the most frequent clinical subtype with 50%. Almost one-third had unaltered electrophysiological studies. Comparative analysis between groups showed statistically significant differences in length of stay, dysautonomia presence, and treatment type. Kaplan-Meier survival analysis showed that 100% of the patients had an independent walk at 3 months. This study reports Mexican MFS patient's characteristics and represents the most extensive case series in Latin America. We observed a high proportion of overlapping syndromes, a good recovery profile, and no significant severe complications.

Antecedent infections in Fisher syndrome: sources of variation in clinical characteristics.

The clinical features of Guillain-Barré syndrome (GBS) are highly variable, according to the type of antecedent infection. Although a major GBS phenotype, Fisher syndrome (FS), has been shown to be preceded by infections similar to those preceding GBS, whether or not the clinical features in FS also vary according to antecedent infection remains unclarified. Frequent antecedent infections among this study of 70 FS patients included Haemophilus influenzae [n = 15 (21%)], Campylobacter jejuni [n = 10 (14%)], and cytomegalovirus (CMV) [n = 6 (8.6%)]. Compared with other FS patients, H. influenzae-seropositive FS patients more frequently had a history of prior upper respiratory tract infection; double vision as the initial symptom; and, except for oculomotor disturbance, more rarely showed cranial nerve involvement. C. jejuni-related FS occurred predominantly in younger male patients and characteristically presented with blurred vision. According to GBS disability scale, CMV-related FS tended to be more severe, although every patient received immunotherapy. Serum anti-GQ1b IgG antibodies were detected in most cases, regardless of antecedent infection type. At the nadir of illness, the most frequent diagnosis in H. influenzae-related cases was "pure FS" without limb weakness or central nervous system involvement (71%), in C. jejuni-related cases "incomplete FS" such as acute ophthalmoparesis with or without ataxia (60%), and in CMV-related cases (50%) advanced conditions such as GBS overlap and Bickerstaff brainstem encephalitis. These findings indicate that the type of preceding infection determined the neurological features of FS. CMV-related FS appeared to be similar to H. influenzae- and C. jejuni-related FS regarding anti-GQ1b antibody-mediated pathogenesis, as opposed to CMV-related GBS.

Clinical characterization of anti-GQ1b antibody syndrome in Korean children.

Anti-GQ1b antibody syndrome encompasses Miller Fisher syndrome and its related disorders. We retrospectively identified 11 pediatric patients (5.4-18 years old) with anti-GQ1b antibody syndrome. Diagnoses of patients included acute ophthalmoparesis (n = 6), classical Miller Fisher syndrome (n = 2), Miller Fisher syndrome/Guillain-Barré syndrome (n = 1), acute ataxic neuropathy (n = 1), and pharyngeal-cervical-brachial weakness (n = 1). Nine patients (81.8%) fully recovered. Maturational change in GQ1b antigen expression and the accessibility of anti-GQ1b antibodies might be the cause of the difference of clinical manifestations in children with anti-GQ1b antibody syndrome.

Atypical clinical manifestations of Miller Fisher syndrome.

Miller Fisher syndrome (MFS) is characterized by a clinical triad of ophthalmoplegia, ataxia, and areflexia, and is closely associated with serum anti-GQ1b antibody. Although the clinical triad is the cardinal diagnostic clue, a variety of other symptoms and signs beyond the triad have been reported. To elucidate the frequency and characteristics of atypical clinical manifestations of MFS, we recruited 38 patients with MFS and evaluated the symptoms or signs beyond the classic triad. Eleven (29%) of 38 patients had atypical clinical manifestations of MFS such as headache (n = 6), delayed facial palsy (n = 3), divergence insufficiency (n = 2), and taste impairment (n = 2). Headache was localized to the periorbital (n = 3), temporal (n = 2), or whole (n = 1) area. Only one of them showed bilateral papilledema and an elevated opening pressure in cerebrospinal fluid analysis. Delayed facial palsy developed after the other signs have reached nadir (n = 1) or started to improve (n = 2), and did not follow a pattern of descending paralysis with other cranial neuropathies. Two patients showed divergence insufficiency without external ophthalmoplegia, and another two had taste impairment over the entire tongue without the other signs of facial and glossopharyngeal nerve involvements. Our study shows that approximately 30% of MFS patients can have atypical clinical manifestations beyond the classic triad. These results reflect the broad clinical spectrum of MFS, and might be associated with the presence of additional antiganglioside antibodies besides anti-GQ1b in patients with MFS.

Bulbar paralysis associated with Miller-Fisher syndrome and its overlaps in Chinese patients.

The study aimed to determine the incidence and the onset time of bulbar paralysis (BP) associated with Miller-Fisher syndrome (MFS) and its overlaps, to better understand the clinical characteristics among patients with MFS and its overlaps. Medical records from 48 patients with MFS and its overlaps were divided into two groups based on the presence (MFS-BP+) or absence (MFS-BP-) of BP. Their clinical features, laboratory and electrophysiological findings, neuroimaging data, and treatment plan were analyzed and compared between two groups. The incidence of BP associated with MFS and its overlaps was 48%. Eighty-two percent of the patients developed BP within 1 week after the onset of MFS and its overlaps. The cerebrospinal fluid (CSF) protein level in patients was higher in MFS-BP+ than in MFS-BP- group (67.69 ± 26.59 vs. 50.15 ± 20.44 mg/dl; P < 0.05). Frequencies of severe limb weakness, hypoglossal paralysis, disturbance of consciousness, and tracheal intubation required were also significantly higher in MFS-BP+ than in MFS-BP- group. Positive results of anti-GQ1b and anti-GT1b antibodies were all found in MFS-BP+ group. The prevalence of BP in MFS and its overlap was higher, the majority of BP occurred within 7 days after the onset of the disease, and early diagnosis of BP concurrence is helpful to decide the treatment plan.

[Acute polyneuropathies in a hospital in the south of Spain: ten years' experience]. / Polineuropatias agudas en un hospital del sur de España: diez años de experiencia.

INTRODUCTION: Guillain-Barre syndrome is the most frequent cause of acute flaccid paralysis in children. AIM: To describe the characteristics of patients diagnosed with acute polyneuropathies and their long-term progress. PATIENTS AND METHODS: We conducted a retrospective descriptive analysis of children under 14 years of age admitted to our hospital between January 2004 and December 2014. Clinical, demographic and neurophysiological variables were collected together with other imaging tests. RESULTS: Twenty-six patients, with a mean age of 3.83 years, were diagnosed with acute polyneuropathies, four of them of Moroccan origin. Twenty of them (76%) had a history of previous infection. The mean time elapsed since the onset of the symptoms until admission to hospital was 9.2 days, and from admission until beginning with gamma globulins it was 1.6 days. The clinical signs and symptoms prior to diagnosis were of a very heterogeneous nature. They all presented muscular weakness; 90% displayed areflexia; and 30% showed involvement of the cranial nerves. All of them (100%) received intravenous gamma globulins, and 38.4% were given systemic corticosteroids. Two patients presented chronification of the pathology. There was no mortality in the series. CONCLUSIONS: The patients included in our study presented very unspecific symptoms in the early phases, which initially led to alternative diagnoses. To avoid this delay in the diagnosis, it is essential to perform an exhaustive physical examination that includes the myotatic reflexes and to maintain a high level of suspicion of the disease even with normal results in the complementary tests if they are performed at an early stage. We detected a greater number of cases of axonal polyneuropathy, which can possibly be explained by the high number of patients of Moroccan origin who were treated.

TITLE: Polineuropatias agudas en un hospital del sur de España: diez años de experiencia.Introduccion. El sindrome de Guillain-Barre es la causa mas frecuente de paralisis flacida aguda en niños. Objetivo. Describir caracteristicas de los pacientes diagnosticados de polineuropatias agudas y su evolucion a largo plazo. Pacientes y metodos. Analisis descriptivo retrospectivo de los menores de 14 años ingresados en nuestro hospital entre enero de 2004 y diciembre de 2014. Se recogieron variables clinicas, demograficas, neurofisiologicas y otras pruebas de imagen. Resultados. Veintiseis pacientes, con una mediana de edad de 3,83 años, fueron diagnosticados de polineuropatias agudas, cuatro de ellos de origen marroqui. Veinte (76%) tenian antecedentes de infeccion previa. El tiempo medio desde el inicio de los sintomas hasta su ingreso fue de 9,2 dias y, desde este hasta el inicio de gammaglobulinas, de 1,6 dias. La sintomatologia que precedio al diagnostico fue de caracter muy heterogeneo. Todos presentaron debilidad muscular; el 90%, arreflexia; y el 30%, afectacion de los pares craneales. El 100% recibio gammaglobulinas intravenosas, y el 38,4%, corticoides sistemicos. Presentaron cronificacion de la patologia dos pacientes. No hubo mortalidad en la serie. Conclusiones. Los pacientes incluidos en nuestro estudio presentaron en fases tempranas sintomas muy inespecificos que llevaron a diagnosticos alternativos iniciales; para evitar este retraso diagnostico, resulta fundamental realizar una exhaustiva exploracion fisica que incluya los reflejos osteotendinosos y mantener un alto indice de sospecha de la enfermedad aun con normalidad en las pruebas complementarias si estas son precoces. Detectamos un mayor numero de polineuropatia axonal, posiblemente explicado por el elevado numero de pacientes atendidos de origen marroqui.

Demyelinating Guillain-Barré syndrome recurs more frequently than axonal subtypes.

Guillain-Barré syndrome (GBS) is considered a monophasic disorder yet recurrences occur in up to 6% of patients. We retrospectively studied an Italian-Japanese population of 236 GBS and 73 Miller Fisher syndrome (MFS) patients and searched for factors which may be associated with recurrence. A recurrent patient was defined as having at least two episodes that fulfilled the diagnostic criteria for GBS and MFS with an identifiable recovery after each episode and a minimum of 2months between episodes. Preceding Campylobacter jejuni (C. jejuni) infection and antiganglioside antibodies were also assessed. Seven (3%) recurrent GBS and one (1.4%) recurrent MFS patients were identified. In the individual patient the clinical features during episodes were usually similar varying in severity whereas the preceding infection differed. None of the patients had GBS in one episode and MFS in the recurrence or vice versa. Recurrent GBS patients, compared with monophasic GBS, did not have preceding diarrhea at the first episode and considering the electrophysiological subtypes, acute inflammatory demyelinating polyneuropathies recurred more frequently than axonal GBS (6.5% vs 0.9%, p=0.04). In conclusion in a GBS population with a balanced number of demyelinating and axonal subtypes less frequent diarrhea and demyelination at electrophysiology were associated with recurrence.

[Fisher Syndrome and Bickerstaff Brainstem Encephalitis].

Fisher syndrome has been regarded as a peculiar inflammatory neuropathy with ophthalmoplegia, ataxia, and areflexia, whereas Bickerstaff brainstem encephalitis has been considered a pure central nervous system disease characterized by ophthalmoplegia, ataxia, and consciousness disturbance. Both disorders share common features including preceding infection, albumin-cytological dissociation, and association with Guillain-Barré syndrome. The discovery of anti-GQ1b IgG antibodies further supports the view that the two disorders represent a single disease spectrum. The lesions in Fisher syndrome and Bickerstaff brainstem encephalitis are presumably determined by the expression of ganglioside GQ1b in the human peripheral and central nervous systems. Bickerstaff brainstem encephalitis is likely to represent a variant of Fisher syndrome with central nervous system involvement.

A multicentre prospective study of Guillain-Barré syndrome in Japan: a focus on the incidence of subtypes.

OBJECTIVE: Guillain-Barré Syndrome (GBS) is classified into the two major subtypes; acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Previous studies have suggested that AIDP is predominant and AMAN is rare in Western countries, whereas AMAN is not always uncommon in East Asia. We aimed to clarify the incidence of the subtypes of GBS in Japan. METHODS: We performed a prospective multicentre survey over 3 years (2007-2010). Clinical and electrophysiological findings were collected from 184 patients with GBS in 23 tertiary neurology institutes. Anti-ganglioside antibodies were measured by ELISA. We also surveyed the incidence of Fisher syndrome (FS). RESULTS: By electrodiagnostic criteria of Ho et al, patients were classified as having AIDP (40%), or AMAN (22%), or unclassified (38%). Anti-GM1 IgG antibodies were found for 47% of AMAN patients, and 18% of AIDP patients (p<0.001). There were no specific regional trends of the electrodiagnosis and anti-GM1 positivity. During the same study period, 79 patients with FS were identified; the percentage of FS cases out of all cases (FS/(GBS+FS)) was 26%. CONCLUSIONS: The frequency of GBS patients with the electrodiagnosis of AMAN by single nerve conduction studies is approximately 20% in Japan, and the AMAN pattern is closely associated with anti-GM1 antibodies. The incidence of FS appears to be much higher in Japan than in Western countries.

[Clinical analyses of recurrence in Guillain-Barré syndrome and Fisher syndrome].

Recurrence of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) is uncommon. We retrospectively studied the cases of 93 consecutive patients with GBS and FS who were admitted to our hospital between January 2000 and March 2013. We analyzed the clinical features of and anti- glycolipid antibodies in patients who experienced recurrence. Of the 93 patients, 53, 37, and 3 had GBS, FS, and overlapping GBS and FS, respectively. There were 6 recurrences in 4 patients, all of whom were women; their onset age ranged from 26 to 51 years, and the average time to recurrence ranged from 9 months to 25 years. The recurrence rate of FS was 10.8%. On the recurrence, 2 patients showed FS (5.4%) and 2 patients showed overlap of GBS and FS (5.4%). All patients with recurrence showed good prognosis and increased anti-GQ1b glycolipid antibody levels both at the initial episode and at recurrence. Immunological examinations, including those for detecting changes in anti-glycolipid antibodies, are important for clarifying the pathomechanism of recurrence in GBS and FS.

Retrospective analysis of Guillain-Barré syndrome and Fisher syndrome after the Great East Japan Earthquake.

Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) are immune-mediated peripheral neuropathies, and most of these cases were known to be associated with a preceding infection. Recent reports evidenced an increase in the number of infectious disease cases after the earthquake. The aim of this report is to investigate the incidence and clinical features of GBS and FS after the Great East Japan Earthquake. We found GBS and FS patients had markedly increased in 2011, the year of the earthquake. In regard to an antecedent illness, gastrointestinal infection was significantly increased in GBS patients after the earthquake. These results suggest environmental factors including infectious agents and stress caused by the earthquake might have been involved in the outbreak of the diseases.

Clinical and electrophysiological features of Guillain-Barré syndrome in Iran.

We evaluated the clinical and electrophysiological characteristics of 121 consecutive patients admitted with Guillain-Barré syndrome (GBS) to a tertiary referral hospital in Tehran, Iran, from 1997 to 2007. The mean age of patients was 38.9 (standard deviation 19.7) years. The predominant subtype of GBS was the demyelinating form. Miller Fisher syndrome was present in 3.3% of patients. There was no significant seasonal clustering among the three subtypes, but axonal variants tend to occur in summer. In contrast with other subtypes, the majority of patients with acute motor-sensory axonal neuropathy (AMSAN) were female (72.3%). AMSAN patients also had significantly longer hospitalization time (p=0.002) and intensive care unit (ICU) admission (p=0.017), while none of the acute motor axonal neuropathy patients needed ICU admission. Involvement of cranial nerves and symmetry of signs were significantly detected in the demyelinating variant (p=0.021 and p=0.040, respectively). The overall mortality was 3.3%.

Pandemic A/H1N1 2009 influenza vaccination, preceding infections and clinical findings in UK children with Guillain-Barré syndrome.

OBJECTIVE: To record clinical findings in all new cases of Guillain-Barré syndrome (GBS) or Fisher syndrome (FS) in UK children in the 2 years following September 2009 and determine the proportion temporally associated with recent infections, pandemic H1N1 (2009) strain influenza vaccination or seasonal influenza vaccination. DESIGN: A prospective UK-wide epidemiological study using the British Paediatric Surveillance Unit system. PATIENTS: Children aged 16 years or less meeting the Brighton Collaboration criteria for GBS or FS. RESULTS: 112 children with GBS (66 boys and 46 girls) and 3 boys with FS were identified in 2 years. All but one recovered sufficiently to go home. The annual UK incidence rate of GBS in patients less than 15 years old was 0.45/100 000, similar to other countries. There was evidence of infection in the 3 months preceding onset in 92/112 GBS and 3/3 FS cases. Of those living in England, 7 cases received pandemic A/H1N1 2009 influenza vaccination before GBS symptom onset (3/7 were within 6 months including 1 within 3 months); 2 children received 2010/2011 seasonal influenza vaccination within 6 months of GBS onset. The numbers vaccinated were not significantly greater than expected by chance. CONCLUSIONS: The outcome for childhood GBS and FS after 6 months was better than reported in adults. Most UK GBS and FS cases had infections in the preceding 3 months. When considering the children living in England, there was no significantly increased risk of GBS after pandemic A/H1N1 2009 influenza vaccination or 2010/2011 seasonal influenza vaccination.