Evaluating yield and utilization of ganglioside antibody testing in clinical practice.

BACKGROUND AND OBJECTIVES: Ganglioside antibodies can help diagnose distinct acute and chronic inflammatory neuropathies including axonal variants of Guillain-Barre syndrome, Miller-Fisher syndrome (MFS), multifocal motor neuropathy, and chronic sensory ataxic neuropathies. Because ganglioside antibody testing may be routinely ordered in patients with suspected inflammatory neuropathy, we sought to evaluate its yield and utilization in clinical practice. METHODS: We performed a retrospective chart review of all patients at London Health Sciences Centre who underwent ganglioside antibody testing between April 2019 and August 2023. The disease phenotype was determined for each patient, and the proportion of all tests that yielded a true-positive result was calculated. Ganglioside antibody positivity was classified as a true-positive result if the disease phenotype was robustly associated with the detected ganglioside antibody and there was no other more likely diagnosis. RESULTS: We identified 92 patients who underwent ganglioside antibody testing. One patient (1%) was classified as having a true-positive result; this patient had GQ1b-IgG positivity with MFS. Among 92 patients tested, 20 patients (22%) had a disease phenotype that was considered to be robustly associated with ganglioside antibody positivity. CONCLUSIONS: The yield of ganglioside antibody testing in clinical practice is low. We found that this testing is frequently ordered in patients with disease phenotypes that are not robustly associated with ganglioside antibody positivity, indicating that suboptimal test utilization is a primary contributor to its low yield. Restricting ganglioside antibody testing to patients with characteristic disease phenotypes would be valuable to improving yield and utilization of this testing.

Only anti-GM4 antibody positivity in a Chinese girl with overlapping MFS/GBS: a case report.

BACKGROUND: Guillain-Barré syndrome (GBS), as the most common cause of acute flaccid paralysis worldwide, is considered a part of a clinical spectrum in which discrete, complete, or incomplete forms of GBS and overlapping syndromes lie on the basis of their clinical features. The term overlapping Miller Fisher syndrome (MFS)/GBS is used when patients with MFS also suffer from progressive motor weakness of the limbs. Anti-ganglioside GQ1b has been specifically associated with MFS and ophthalmoplegia. CASE DESCRIPTION: Here, we report a Chinese girl who was diagnosed with overlapping MFS/GBS showing acute flaccid paralysis of all four limbs, sensory symptoms, cranial nerve dysfunction, autonomic involvement, ophthalmoplegia, and ataxia. She had high serum and cerebrospinal fluid titres of monospecific anti-GM4 IgG antibody instead of anti-GQ1b antibody in the acute phase. CONCLUSION: Anti-GM4 antibodies usually coexist with other antiganglioside antibodies, leading to missed diagnoses. The findings of the present study show that antibodies to ganglioside GM4 may in overlapping MFS/GBS as the lone immunological factors.

Retrospective analysis of COVID-19 patients with Guillain-Barre, Miller-Fisher, and opsoclonus-myoclonus-ataxia syndromes-a case series.

BACKGROUND: In accordance with the rising number of SARS-CoV­2 infections, reports of neurological complications have also increased. They include cerebrovascular diseases but also immunological diseases such as Guillain-Barre syndrome (GBS), Miller-Fisher syndrome (MFS), and opsoclonus-myoclonus-ataxia syndrome (OMAS). While GBS and MFS are typical postinfectious complications, OMAS has only recently been described in the context of COVID-19. GBS, MFS, and OMAS can occur as para- and postinfectious, with different underlying pathomechanisms depending on the time of neurological symptom onset. The study aimed to describe clinical features, time between infection and onset of neurological symptoms, and outcome for these diseases. METHODS: All COVID-19 patients treated in the neurological ward between January 2020 and December 2022 were screened for GBS, MFS, and OMAS. The clinical features of all patients, with a particular focus on the time of onset of neurological symptoms, were analyzed. RESULTS: This case series included 12 patients (7 GBS, 2 MFS, 3 OMAS). All GBS and one MFS patient received immunomodulatory treatment. Three patients (2 GBS, 1 OMAS) had a severe COVID-19 infection and received mechanical ventilation. In patients with OMAS, only one patient received treatment with intravenous immunoglobulin and cortisone. The remaining two patients, both with disease onset concurrent with SARS-COV­2 infection, recovered swiftly without treatment. In all subgroups, patients with concurrent onset of neurological symptoms and COVID-19 infection showed a trend toward shorter disease duration. CONCLUSION: All patient groups displayed a shorter disease duration if the onset of neurological symptoms occurred shortly after the COVID-19 diagnosis. In particular, both the OMAS patients with symptom onset concurrent with COVID-19 showed only abortive symptoms followed by a swift recovery. This observation would suggest different pathomechanisms for immune-mediated diseases depending on the time of onset after an infection.

Delayed onset Bickerstaff brainstem encephalitis overlapping Miller-Fisher Syndrome during SARS-CoV-2 infection.

Bickerstaff brainstem encephalitis (BBE) is a neuroimmunologic disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance, mostly subsequent to an infection. BBE is considered to be a variant of Miller-Fisher syndrome (MFS), which also exhibits external ophthalmoplegia and ataxia but not presenting consciousness alterations. Therefore, these two medical conditions are included in the clinical spectrum of the "Fisher-Bickerstaff syndrome" ( Shahrizaila and Yuki in J Neurol Neurosurg Psychiatry 84(5):576-583) [1]. With regard to the etiopathogenesis, increasing evidence worldwide suggests that SARS-CoV-2 infection-enhanced immune response is involved in a wide range of neurological complications such as Guillain-Barré syndrome (GBS), MFS, acute necrotizing encephalitis (ANE), myelitis, acute disseminated encephalomyelitis (ADEM), and, although very rarely, BBE either (Hosseini et al. in Rev Neurosci 32:671-691) [2]. We report a case of a patient affected by delayed onset BBE overlapping MFS during a mild SARS-CoV-2 infection. To the best of our knowledge, similar cases have never been reported.

Miller-Fisher syndrome with positive anti-GD1b and anti-GM1 antibodies combined with multiple autoimmune antibodies: A case report.

RATIONALE: Anti-ganglioside antibodies (AGA) play an essential role in the development of Miller-Fisher syndrome (MFS). The positive rate of ganglioside antibodies was exceptionally high in MFS, especially anti-GQ1b antibodies. However, the presence of other ganglioside antibodies does not exclude MFS. PATIENT CONCERNS: We present a 48-year-old male patient who suddenly developed dizziness, visual rotation, nausea, and vomiting accompanied by unsteady gait and diplopia for 3 days before presentation to our clinic. DIAGNOSES: On physical examination, the patient's right eye could not fully move to the right side and horizontal nystagmus was found. Coordination was also impaired in the upper and lower extremities with dysmetria and dysdiadochokinesia. The electromyography and cerebrospinal fluid examination results were normal. The serum anti-GQlb antibody test results were negative. However, serum anti-GD1b IgM and anti-GM1 IgM antibodies were positive. Meanwhile, the anti-thyroid peroxidase antibody was >600.00 IU/mL (0.00-34.00), and the anti-SS-A/Ro52 antibody was positive. He was diagnosed with MFS. INTERVENTIONS: The patient received IVIg treatment for 5 days (0.4 g/kg/day) from day 2 to day 6 of hospitalization. On the 7th day of admission, the patient was administered intravenous methylprednisolone (500 mg/day), which was gradually reduced. OUTCOMES: The patient's symptoms improved after treatment with immunoglobulins and hormones. LESSONS: We report a case of MFS with positive anti-GD1b and anti-GM1 antibodies combined with multiple autoimmune antibodies. Positive ganglioside antibodies may be used as supporting evidence for the diagnosis; however, the diagnosis of MFS is more dependent on clinical symptoms.

Clinical characteristics and prognosis of temporary miller fisher syndrome following COVID-19 vaccination: a systematic review of case studies.

BACKGROUND: Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome (GBS) which is characterized by the three components of ophthalmoplegia, ataxia, and areflexia. Some studies reported MFS as an adverse effect of the COVID-19 vaccination. We aimed to have a detailed evaluation on demographic, clinical, and para-clinical characteristics of subjects with MFS after receiving COVID-19 vaccines. MATERIALS AND METHODS: A thorough search strategy was designed, and PubMed, Web of Science, and Embase were searched to find relevant articles. Each screening step was done by twice, and in case of disagreement, another author was consulted. Data on different characteristics of the patients and types of the vaccines were extracted. The risk of bias of the studies was assessed using Joanna Briggs Institute (JBI) tools. RESULTS: In this study, 15 patients were identified from 15 case studies. The median age of the patients was 64, ranging from 24 to 84 years. Ten patients (66.6%) were men and Pfizer made up 46.7% of the injected vaccines. The median time from vaccination to symptoms onset was 14 days and varied from 7 to 35 days. Furthermore,14 patients had ocular signs, and 78.3% (11/14) of ocular manifestations were bilateral. Among neurological conditions, other than MFS triad, facial weakness or facial nerve palsy was the most frequently reported side effect that was in seven (46.7%) subjects. Intravenous immunoglobulin (IVIg) was the most frequently used treatment (13/15, 86.7%). Six patients received 0.4 g/kg and the four had 2 g/kg. Patients stayed at the hospital from five to 51 days. No fatal outcomes were reported. Finally, 40.0% (4/15) of patients completely recovered, and the rest experienced improvement. CONCLUSION: MFS after COVID-19 immunization has favorable outcomes and good prognosis. However, long interval from disease presentation to treatment in some studies indicates that more attention should be paid to MFS as the adverse effect of the vaccination. Due to the challenging diagnosis, MFS must be considered in list of the differential diagnosis in patients with a history of recent COVID-19 vaccination and any of the ocular complaints, ataxia, or loss of reflexes, specially for male patients in their 60s and 70s.

[Guillain-Barré syndrome and its variants: Miller-Fisher syndrome. Description of a clinical case in pediatric age.] / La sindrome di Guillain-Barré e le sue varianti: la sindrome di Miller-Fisher. Descrizione di un caso clinico in età pediatrica.

Miller-Fisher syndrome is a rare acquired nerve disease related to Guillain-Barré syndrome. Clinical features include asthenia, ocular muscle weakness with ophthalmoplegia, impaired limb coordination with instability, and absence of tendon reflexes. Swallowing disorders and rarely respiratory failure may be associated. The article aims to summarize, starting from the presentation of a clinical case, the latest updates which, in clinical practice, can be useful for a correct diagnosis and treatment of this condition which concerns both adult and pediatric patients.

Anti-GT1a and anti-GQ1b immunoglobulin G antibody positivity with overlapping Miller Fisher/Guillain-Barré syndromes and prominent headache: a case report.

Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are acute immune-mediated peripheral neuropathies. In addition to their classic presentations, a variety of other signs and symptoms have been reported; however, headache appears to be relatively uncommon. We describe a 53-year-old woman who presented with acute bulbar palsy as the first symptom of overlapping MFS/GBS accompanied by severe headache. The first important clinical impairment of the patient was acute bulbar palsy along with prominent headache, without limb weakness. Although her initial diagnosis was acute bulbar palsy plus, she subsequently developed lower limb diffuse weakness, and her final clinical diagnosis was overlapping MFS/GBS. Anti-ganglioside antibodies were positive for anti-GQ1b and anti-GT1a immunoglobulin G. The patient received intravenous immunoglobulin on day 2 of admission. Early identification of these overlapping syndromes is important for the management of patients, to avoid respiratory failure or severe weakness with axonal degeneration. We therefore remind clinicians of the importance of further examination in patients with headache and acute bulbar palsy of unknown origin.

CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome.

BACKGROUND AND OBJECTIVES: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study. METHODS: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/µL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%). RESULTS: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/µL in 1,005 patients (83%), 5-49 cells/µL in 200 patients (16%), and ≥50 cells/µL in 13 patients (1%). DISCUSSION: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/µL, is compatible with GBS after a thorough exclusion of alternative diagnoses. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS.

A Case with Anti-ganglioside Antibodies Showing Multiple Cranial Nerve Palsies Detected on Gadolinium-enhanced Magnetic Resonance Imaging.

The anti-GQ1b IgG antibody is often accompanied by other anti-ganglioside antibodies, which induces various neurological symptoms. We herein report a patient with anti-ganglioside antibodies, including anti-GQ1b IgG and anti-GT1a IgG antibodies, showing bilateral ophthalmoplegia, facial nerve palsies, dysarthria, dysphagia, dysesthesia in both hands, and enhancement of the bilateral oculomotor, abducens, and facial nerves on gadolinium (Gd)-enhanced T1-weighted brain magnetic resonance imaging (MRI). He was first treated with intravenous immunoglobulin, which improved ophthalmoplegia, bulbar palsies, and dysesthesia of hands, but the facial nerve palsies worsened, and Gd enhancement of the brain nerves persisted. High-dose methylprednisolone therapy subsequently improved the facial nerve palsies and Gd enhancement of the cranial nerves. This is the first case with anti-ganglioside antibodies presenting with multiple cranial nerve palsies that was followed to track the changes in the Gd enhancement of cranial nerves on MRI.

A Case of Miller Fisher Syndrome with Cerebellar Hypoperfusion.

We report a case of a 76-year-old man with Miller Fisher syndrome presenting with acute ophthalmoplegia and ataxia. Cerebrospinal fluid analysis showed normocytosis with an increased protein level. Serum anti-GQ1b IgG and anti-GT1a IgG antibodies were positive. Based on these results, the patient was diagnosed with Miller Fisher syndrome. He was treated with two courses of intravenous immunoglobulin, which improved his neurological symptoms. Brain perfusion single-photon emission computed tomography showed that cerebellar blood flow was decreased in the acute stage of the disease and improved after treatment. Although the prevailing view is that ataxia in Miller Fisher syndrome patients is of a peripheral origin, this case suggests that cerebellar hypoperfusion contributes to the development of ataxia in Miller Fisher syndrome.

Acute comitant strabismus in anti-GQ1b antibody syndrome.

Ophthalmoplegia is the diagnostic hallmark of anti-GQ1b antibody syndrome. This study aimed to define the patterns of acute comitant strabismus in patients with anti-GQ1b antibody syndromes. We retrospectively analyzed the ocular motor findings in 84 patients with anti-GQ1b antibody-associated ophthalmoplegia during the acute phases. Of the 84 patients, 11 (13%) showed acute comitant strabismus. Compared to those without, patients with acute comitant strabismus frequently showed abnormal ocular motor findings that included gaze-evoked (n = 8), spontaneous (n = 4) and positional nystagmus (n = 4), saccadic hypermetria (n = 3), head-shaking nystagmus (n = 2), pulse-step mismatch (n = 1), and impaired visual cancellation of the vestibulo-ocular reflex (n = 1, p < 0.001). On the contrary, iridoplegia (p = 0.029) and ptosis (p = 0.001) were more commonly observed in patients with paralytic (incomitant) strabismus than in those with acute comitant strabismus. Comitant strabismus can manifest during the acute phase of anti-GQ1b antibody syndromes in association with other central ocular motor abnormalities. These findings implicate that the cerebellum and/or brainstem can be the primary target of the anti-GQ1b antibodies.

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.

Bickerstaff's brainstem encephalitis mimicking herpetic encephalomyelitis in a liver transplant patient with anti-GQ1b antibodies.

A woman in her late 70s with a history of liver transplant presented with ophthalmoplegia, ataxia, areflexia, positive Babinski's sign and reduced consciousness. This followed an antecedent illness in the form of a herpes zoster infection. MRI of the brain/spinal cord, cerebrospinal fluid analysis with viral PCR and routine blood tests were normal, and tacrolimus neurotoxicity was ruled out. Serum anti-GQ1b antibodies were positive. A diagnosis of Bickerstaff's brainstem encephalitis was made, forming part of the continuum that involves Miller-Fisher syndrome, entitled the 'anti-GQ1b syndrome'. Complete recovery ensued without intravenous immunoglobulins or plasma exchange. The role of monitoring anti-ganglioside pattern change to predict or confirm disease recurrence and disease severity is further discussed.

Acute Isolated External Ophthalmoplegia: Think of Anti-GQ1b Antibody Syndrome.

Acute-onset ophthalmoplegia is a perplexing diagnosis in a young child. When the full-blown picture of ophthalmoplegia, ataxia, and areflexia is evident, the diagnosis of Miller-Fisher syndrome (MFS), a variant of Guillain-Barre syndrome (GBS), is almost certain. However, the same is not true for isolated external ophthalmoplegia as it is etiologically heterogeneous. Only anecdotal case reports of childhood-onset acute ophthalmoplegia exist in the literature. Adult series suggest that acute onset external ophthalmoplegia is often immune-mediated and is secondary to anti-GQ1b antibodies. We present a 30-month-old boy with acute-onset bilateral external ophthalmoplegia with highly elevated serum anti-GQ1b antibodies. The child had a rapid and complete recovery with intravenous immunoglobulin. A review of all published cases of childhood anti-GQ1b antibody syndrome was performed. The case highlights that anti-GQ1b antibody syndrome should be considered even in young children with acute-onset external ophthalmoplegia. The disease has a favorable prognosis. The majority improve on conservative management. Treatment with steroids or IVIG may be considered in some after weighing the risks and benefits.

A teenager with ophthalmoparesis and dysphagia.

The pharyngeal-cervical-brachial (PCB) variant is a rare presentation of Guillain-Barré syndrome (GBS), and there is a handful of case reports that overlap with the Miller-Fisher syndrome (MFS) variant of GBS. This overlap produces varied symptoms that may be confusing and challenging for physicians to diagnose timely and start appropriate treatment. In this article, we present a case report and review of the rare overlap of the PCB variant with the MFS variant of GBS.