Role of inhibitory B cell co-receptors in B cell self-tolerance to non-protein antigens.

Antibodies to non-protein antigens such as nucleic acids, polysaccharides, and glycolipids play important roles in both host defense against microbes and development of autoimmune diseases. Although non-protein antigens are not recognized by T cells, antibody production to non-protein antigens involve T cell-independent mechanisms such as signaling through TLR7 and TLR9 in antibody production to nucleic acids. Although self-reactive B cells are tolerized by various mechanisms including deletion, anergy, and receptor editing, T cell tolerance is also crucial in self-tolerance of B cells to protein self-antigen because self-reactive T cells induce autoantibody production to these self-antigens. However, presence of T cell-independent mechanism suggests that T cell tolerance is not able to maintain B cell tolerance to non-protein self-antigens. Lines of evidence suggest that B cell response to non-protein self-antigens such as nucleic acids and gangliosides, sialic acid-containing glycolipids, are suppressed by inhibitory B cell co-receptors CD72 and Siglec-G, respectively. These inhibitory co-receptors recognize non-protein self-antigens and suppress BCR signaling induced by these antigens, thereby inhibiting B cell response to these self-antigens. Inhibitory B cell co-receptors appear to be involved in B cell self-tolerance to non-protein self-antigens that can activate B cells by T cell-independent mechanisms.

Expanding our understanding of Guillain-Barré syndrome: Recent advances and clinical implications.

Guillain-Barré syndrome (GBS) is a rare yet potentially life-threatening disorder of the peripheral nervous system (PNS), characterized by substantial clinical heterogeneity. Although classified as an autoimmune disease, the immune mechanisms underpinning distinct GBS subtypes remain largely elusive. Traditionally considered primarily antibody-mediated, the pathophysiology of GBS lacks clarity, posing challenges in the development of targeted and effective treatments. Nevertheless, recent investigations have substantially expanded our understanding of the disease, revealing an involvement of autoreactive T cell immunity in a major subtype of GBS patients and opening new biomedical perspectives. This review highlights these discoveries and offers a comprehensive overview of current knowledge about GBS, including ongoing challenges in disease management.

Clinical application of phage immunoprecipitation sequencing to diagnose enterovirus D68 as the underlying etiology in a case of Gullain-Barré syndrome.

Gullain-Barré syndrome (GBS) is an acute peripheral neuropathy often preceded by respiratory or gastrointestinal infections, though molecular testing of cerebrospinal fluid (CSF) is often inconclusive. In a recent case of severe pediatric GBS in British Columbia, Canada, we detected CSF antibodies against enterovirus D (EV-D) to link GBS with prior EV-D68 respiratory infection.

Relationship between Guillain-Barré syndrome and Cardiovascular disease: A bidirectional Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Guillain-Barré syndrome (GBS) and cardiovascular diseases (CVDs) have been observed to have a potential association, with GBS potentially leading to cardiovascular complications. However, these observational studies may be influenced by confounding factors. This study aimed to assess the causal relationship between GBS and CVDs, including heart failure (HF), atrial fibrillation (AF), and coronary artery disease (CAD), using a two-sample bidirectional Mendelian randomization (MR) analysis. METHODS: Datasets for GBS and CVDs were retrieved from the United Kingdom Biobank and analyzed using selected instrumental variables (IVs) related to genetic variations. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the reliability of the selected IVs. The analysis results were then visualized to illustrate the causal relationships. RESULTS: The study identified genetic variants as IVs for both GBS and CVDs. MR analysis revealed a significant causal effect of GBS on the increased risk of HF (Inverse variance weighted [IVW], p<0.05), but no significant causal relationship was found between GBS and AF or CAD. Similarly, no causal effect of CVDs on the occurrence of GBS was observed. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy, supporting the robustness of the results. CONCLUSION: This bidirectional MR analysis suggests a causal relationship between GBS and an increased risk of HF but not with AF or CAD, nor was a reverse causal effect of CVDs on GBS observed. These findings underscore the importance of considering cardiovascular complications, particularly HF, in the clinical management of patients with GBS in European populations.

P2X7 receptor antagonists modulate experimental autoimmune neuritis via regulation of NLRP3 inflammasome activation and Th17 and Th1 cell differentiation.

BACKGROUND: Guillain-Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system. METHODS: Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4+ T cells, CD8+ T cells, and macrophages within the sciatic nerves and spleens of rats using immunofluorescence labeling and flow cytometry. The P2X7R antagonist brilliant blue G (BBG) was employed to examine its therapeutic impact on rats with experimental autoimmune neuritis (EAN) induced by immunization with the P0180 - 199 peptide. We analyzed CD4+ T cell differentiation in splenic mononuclear cells using flow cytometry, assessed Th17 cell differentiation in the sciatic nerve through immunofluorescence staining, and examined the expression of pro-inflammatory cytokine mRNA using RT-PCR. Additionally, we performed protein blotting to assess the expression of P2X7R and NLRP3-related inflammatory proteins within the sciatic nerve. Lastly, we utilized flow cytometry and immunofluorescence labeling to examine the expression of NLRP3 on CD4+ T cells in rats with EAN. RESULTS: P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats. CONCLUSIONS: Suppression of P2X7R relieved EAN manifestation by regulating CD4+ T cell differentiation and NLRP3 inflammasome activation. This finding underscores the potential significance of P2X7R as a target for anti-inflammatory treatments, advancing research and management of GBS.

Explore genetic susceptibility association between viral infections and Guillain-Barré syndrome risk using two-sample Mendelian randomization.

BACKGROUND: Numerous observational studies have indicated that patients with Guillain-Barré syndrome (GBS) frequently had infections with various pathogens before the onset of the disease, particularly several viral infections. Some of these infections are linked to specific clinical and immunological subgroups of GBS, suggesting a potential correlation between viral infections and the development of GBS. However, observational studies have several limitations, including the presence of confounding factors. METHOD: We explored the potential correlation between HIV, SARS-CoV-2, varicella-zoster virus, herpes simplex virus, Epstein-Barr virus, hepatitis B virus, and influenza virus with GBS using a two-sample Mendelian randomization approach. The data was derived from published summary statistics from genome-wide association studies (GWAS). After removing linkage disequilibrium, selecting strong instrumental variables and addressing confounding factors, we would conduct a two-sample Mendelian randomization analysis along with sensitivity testing and the MR-Steiger directional test. RESULT: HIV may have a causal association with GBS (IVW: p = 0.010, OR [95% CI] 1.240 [1.052-1.463]), while no such relationship exists with COVID-19 (IVW: p = 0.275, OR [95% CI] 0.831[0.596-1.159]), varicella (IVW: p = 0.543, OR [95% CI] 0.919 [0.701-1.206]), herpes zoster (IVW: p = 0.563, OR [95% CI] 0.941 [0.766-1.156]), HSV (IVW: p = 0.280, OR [95% CI] 1.244 [0.837-1.851]), EBV (IVW: p = 0.218, OR [95% CI] 0.883 [0.724-1.076]), HBV (IVW: p = 0.179, OR [95% CI] 1.072 [0.969-1.187]), or influenza virus (IVW: p = 0.917, OR [95% CI] 0.971 [0.553-1.703]). We did not find any abnormal SNPs, pleiotropy, or heterogeneity, nor is there any reverse causation. CONCLUSION: Our study results indicate a causal relationship between HIV and GBS, providing new research directions for the etiology of GBS.

The ligand interactions of B cell Siglecs are involved in the prevention of autoimmunity to sialylated self-antigens and in the quality control of signaling-competent B cells.

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of membrane molecules that recognize sialic acid. Most of them are inhibitory receptors that inhibit immune-cell activation by recognizing sialic acid as a self-motif. Human B cells express CD22 (also known as Siglec-2), Siglec-5, Siglec-6 and Siglec-10 whereas mouse B cells express CD22 and Siglec-G (ortholog of human Siglec-10). Siglecs recognize both sialylated molecules expressed on the same cell (cis-ligands) and those expressed by other cells (trans-ligands). In Guillain-Barré syndrome (GBS), antibody production to gangliosides (which are sialic acid-containing glycolipids) expressed by neurons plays a pathogenic role. A Siglec-10 variant deficient in recognition of gangliosides is genetically associated with GBS, suggesting that Siglec-10 induces self-tolerance to gangliosides by recognizing gangliosides as trans-ligands. Recognition of the BCR as a cis-ligand by Siglec-G and CD22 suppresses BCR signaling in B-1 cells and conventional B cells, respectively. This signal suppression prevents excess expansion of B-1 cells and is involved in the quality control of signaling-competent B cells by setting a threshold for tonic signaling during B cell development. CD22 recognizes other cis-ligands including CD22 and ß7 integrin. Interaction of CD22 with other CD22 molecules induces CD22 clustering that suppresses CD22-mediated signal inhibition upon BCR ligation, and interaction with ß7 integrin maintains its function in the gut-homing of B cells. Taken together, interactions of B cell Siglecs with multiple trans- and cis-ligands play important roles in B cell homeostasis and immune responses.

Role of prazosin in patients with Guillain-Barré syndrome with sympathetic overactivity: A cohort study.

INTRODUCTION/AIMS: In Guillain-Barré syndrome (GBS), patients with dysautonomia demonstrate sympathetic overactivity (SO). This study assessed the role of prazosin (α1-blocker) in the management of SO. METHODS: This cohort study was conducted from January 2022 to September 2023. Thirty-two GBS patients with SO received prazosin (2.5-10 mg three times a day) (prazosin group). For comparison, we included historical controls that included 33 GBS patients having SO with similar baseline characteristics, including median age and disability, who did not receive prazosin, from a GBS registry of patients admitted during February 2018-December 2021. The primary endpoint was days to resolution of SO. Secondary endpoints were daily fluctuations in the systolic (SBP) and diastolic blood pressure (DBP), duration of hospital stay, in-hospital mortality, and disability at 3 months. RESULTS: The median ages of both the treatment and the control groups were 36 (IQR 25-49) years and 43 (66.2%) were males. The demographic and clinical parameters were comparable. Prazosin resulted in significantly earlier normalization of SO compared to the control group (median 15 vs. 20 days; p = .01). The mean fluctuations in the SBP and DBP at 15 days were significantly lower in the prazosin group. However, the duration of hospital stay and good recovery at 3 months were comparable. Three patients developed hypotension, while two patients died (ventilator-associated pneumonia) in the prazosin group. DISCUSSION: This study provides new evidence supporting the role of prazosin in SO, and needs randomized trials to confirm our findings.

Utilizing nerve conduction studies to identify very early Guillain-Barré syndrome and distinguish it from mimics in emergency settings.

INTRODUCTION/AIMS: Accurately diagnosing Guillain-Barré syndrome (GBS) in its early stages and distinguishing it from mimics poses challenges. This study aimed to evaluate the utility of an existing electrodiagnostic criterion in very early GBS (VEGBS) for discerning mimics. Additionally, we explored specific electrophysiological abnormalities in VEGBS to design a new diagnostic criterion for more accurate VEGBS diagnosis. METHODS: We retrospectively identified all patients with flaccid quadriparesis initially suspected of GBS who underwent nerve conduction studies (NCS) ≤4 days from symptom onset. We then retrieved their NCS data and applied an existing electrodiagnostic criterion for sensitivity and specificity analyses based on the final discharge diagnosis. Furthermore, we designed a new criterion based on the observed electrophysiological abnormalities that have maximum specificity and at least 50% sensitivity. RESULTS: Among 70 patients suspected of VEGBS, 44 (63%) received a final diagnosis of GBS, while in 26 (37%), the GBS diagnosis was later refuted. Umapathi's definite criterion exhibited a sensitivity of 61.36% and a specificity of 92.31%. The probable and possible groups showed very high sensitivity (90.91% and 100%, respectively); however, specificity was low (57.69% and 30.77%, respectively) in the very early stage. Our proposed criterion demonstrated a sensitivity of 88.64% (CI: 75.44%-96.21%) and a specificity of 96.15% (CI: 80.36%-99.90%). DISCUSSION: The criterion based on presumed electrophysiological correlates of specific early GBS pathophysiology proved more effective than the existing electrodiagnostic criterion in differentiating VEGBS from mimics.

Intravenous immunoglobulin and plasma exchange prescribing patterns for Guillain-Barre Syndrome in the United States-2001 to 2018.

INTRODUCTION/AIMS: Randomized controlled trials show that repeat intravenous immunoglobulin (IVIG) dosing and plasma exchange (PLEX) followed by IVIG (combination therapy) have no additional therapeutic benefit in Guillain-Barre Syndrome (GBS) non-responders. Furthermore, the delineation between GBS and Acute Onset CIDP (A-CIDP) can be particularly challenging and carries therapeutic implications. We aimed to evaluate the presence of repeat IVIG, combination therapy, and diagnostic reclassification from GBS to CIDP. METHODS: We performed a retrospective study of a large healthcare database for patients with GBS in the US from 2001 to 2018. We identified individuals initially diagnosed with GBS and later re-classified as CIDP. Multivariable logistic regression models were developed to determine associations between patient factors and repeat IVIG dosing, combination therapy, and diagnostic re-classification from GBS to CIDP. RESULTS: We identified 2325 patients with GBS. A total of 39.7% received repeat IVIG and 6.1% received combination therapy. The proportion of individuals initially diagnosed with GBS and then re-classified as CIDP was 32.0%. Repeat IVIG, combination therapy, and diagnostic reclassification remained stable over time. Female sex (OR 0.79, 95% CI 0.65-0.96) and medium-high net worth (OR 0.64, 95% CI 0.45-0.90) associated with repeat IVIG therapy, while Asian ethnicity associated with diagnostic re-classification from GBS to CIDP (OR 1.77, 95% CI 1.09-2.86). DISCUSSION: Repeat IVIG dosing was quite common in GBS before newer trials suggesting harm in non-responders, and IVIG/PLEX combination therapy continues to persist despite strong evidence against use in non-responders. Further, nearly one in three patients initially diagnosed with GBS is subsequently diagnosed with CIDP, but the reasons are unclear.

Timing of intravenous immunoglobulin treatment and outcome in Guillain-Barré syndrome: Is time nerve?

INTRODUCTION/AIMS: Despite treatment, a considerable proportion of patients with Guillain-Barré syndrome (GBS) experience poor recovery, highlighting a therapeutic need. There is a lack of evidence that treatment timing affects recovery. This study aims to investigate the effects of intravenous immunoglobulin (IVIg) timing on disability and speed of recovery in GBS. METHODS: We performed a retrospective study of 136 IVIg-treated GBS patients admitted to two Korean centers between 2010 and 2021. We analyzed the effect of time to IVIg on the GBS disability scale (GBS-DS) and the degree of improvement from nadir (∆GBS-DS) at 1, 3, 6, and 12 months, as well as the time to regain the ability to walk or run unaided. Time to IVIg was treated either as a continuous variable or categorized into 1-week intervals to explore critical time windows. Known prognostic factors, the modified Erasmus GBS Outcome Scores on admission and pre-treatment serum albumin levels were adjusted as covariates. RESULTS: Shorter time to IVIg was independently associated with better GBS-DS, greater ∆GBS-DS, and shorter time to walk or run unaided at all time points. The therapeutic effect of IVIg was notably diminished when administered beyond the first 2 weeks of onset. DISCUSSION: Our study highlights the timing of IVIg as a modifiable prognostic factor in GBS. The earlier IVIg is initiated, the better the outcomes, with the ideal time window being within the first 2 weeks. These findings underscore the importance of prompt diagnosis and early intervention to optimize recovery in GBS patients.

Guillain-Barré syndrome: History, pathogenesis, treatment, and future directions.

BACKGROUND AND PURPOSE: Since its description by Guillain, Barré, and Strohl in 1916, Guillain-Barré syndrome (GBS) has attracted a large literature. The author reviews the history of research into its pathogenesis and treatment to highlight promising avenues for future research. METHODS: This is a nonsystematic personal review. RESULTS: Since the early 1900s, the clinical picture of GBS has been illustrated in multiple series culminating in the ongoing International Guillain-Barré Syndrome study of 2000 patients. In the 1950s and 1960s, the inflammatory nature of the commonest form, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), was described. In the 1990s, two axonal forms, acute motor-sensory axonal neuropathy and acute motor axonal neuropathy, were recognized. In the 1990s and early 2000s, these forms were shown to be due to antibodies against Campylobacter jejuni glycans cross-reacting with glycolipids on axonal membranes. The pathogenesis of AIDP remains unknown, but T-cell responses to the compact myelin proteins, P2 and P0, which cause experimental autoimmune neuritis, suggest that T cells are important. Randomized controlled trials in the 1970s and 1980s showed no benefit from corticosteroids. Trials in the 1980s showed benefit from plasma exchange and in the 1990s from intravenous immunoglobulin. CONCLUSIONS: Future research should seek biomarkers to identify subgroups with different treatment responses, define the true natural history of the disease with population-based epidemiological studies, study the pathology in autopsies early in the disease, seek causative antibodies and confirm autoimmune T-cell responses in AIDP, and expand treatment trials to include anti-T-cell agents.

Antiganglioside antibody frequency in routine clinical care settings.

BACKGROUND AND PURPOSE: Antiganglioside antibodies (AGAs) might be involved in the etiopathogenesis of many neurological diseases, such as Miller-Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS). Available comprehensive reference data regarding AGA positivity rates and cross-responsiveness among AGAs (where one line immunoblot is positive for ≥1 AGA) during routine clinical care are scant. METHODS: In this 10-year monocentric retrospective study, 3560 immunoglobulin (Ig) G and IgM line blots (GA Generic Assays' Anti-Ganglioside Dot kit) obtained using cerebrospinal fluid (CSF) and serum samples from 1342 patients were analyzed for AGA positivity in terms of 14 diagnosis categories and AGA cross-responsiveness. RESULTS: Of all 3560 line blots 158 (4.4%) and of all CSF samples 0.4% (4/924) CSF line blots were AGA positive. For serum IgG, blots with positivity rates higher than the standard deviation of 15.6% were associated with MFS (GD3, GD1a, GT1a and GQ1b) and acute motor axonal neuropathy (AMAN) (GM1, GD1a and GT1a). For serum IgM, blots with positivity rates higher than the standard deviation of 8.1% were associated with AMAN (GM2, GT1a and GQ1b), MFS (GM1, GT1a and GQ1b), multifocal motor neuropathy (MMN) (GM1, GM2 and GQ1b) and chronic inflammatory demyelinating polyneuropathy (CIDP) (GM1). Cross-responsiveness was observed in 39.6% of all positive serum AGA. CONCLUSIONS: Testing for AGAs during routine clinical care rarely led to positive findings, both in serum and even less in CSF, except for the diagnoses AMAN, MFS, MMN and CIDP. Nonspecific findings found as cross-responsiveness between different AGA samples occur frequently, impacting the positivity of most AGA subtypes.

Guillain-Barré syndrome: a comprehensive review.

Guillain-Barré syndrome (GBS) is a potentially devastating yet treatable disorder. A classically postinfectious, immune-mediated, monophasic polyradiculoneuropathy, it is the leading global cause of acquired neuromuscular paralysis. In most cases, the immunopathological process driving nerve injury is ill-defined. Diagnosis of GBS relies on clinical features, supported by laboratory findings and electrophysiology. Although previously divided into primary demyelinating or axonal variants, this dichotomy is increasingly challenged, and is not endorsed by the recent European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines. Intravenous immunoglobulin and plasma exchange remain the primary modalities of treatment, regardless of the electrophysiological subtype. Most patients recover, but approximately one-third require mechanical ventilation, and 5% die. Disease activity and treatment response are currently monitored through interval neurological examination and outcome measures, and the potential role of fluid biomarkers is under ongoing scrutiny. Novel potential therapies for GBS are being explored but none have yet modified clinical practice. This review provides a comprehensive update on the pathological and clinical aspects of GBS for clinicians and scientists.

A nationwide Guillain-Barré syndrome epidemiological study in Spain during the COVID-19 years.

BACKGROUND AND PURPOSE: The purpose was to perform a nationwide epidemiological study of Guillain-Barré syndrome (GBS) in Spain, analysing background incidences and seasonal variation and trying to identify incidence changes during the coronavirus disease 2019 (COVID-19) years. METHODS: This was an observational study collecting all GBS diagnoses from the National Epidemiological Surveillance Network collected by the Ministry of Health. Patients discharged with GBS as the main diagnosis and admitted during 2018-2021 were included. Data on the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were obtained from the National Epidemiology Centre. RESULTS: In total, 3147 cases were included, 832 in 2018, 861 in 2019, 670 in 2020 and 784 in 2021. Nationwide hospital incidence was 1.78 in 2018, 1.71 in 2019, 1.41 in 2020 and 1.66 in 2021, with an increased frequency in males, the elderly population and in the winter season. Eleven per cent of GBS patients needed ventilatory support. GBS and SARS-CoV-2 incidences did not correlate with one another (r = -0.29, p = 0.36). GBS incidence decreased during 2020 and during the COVID-19 lockdown period in comparison to the same months of 2018-2019. CONCLUSIONS: The incidence of GBS in Spain is similar to that of other countries. Despite prior reports describing a significant increase in COVID-19-associated GBS in Spain, a significant drop of GBS incidence during the SARS-CoV-2 pandemic was detected, probably due to prevention measures.

Neuropathies related to hepatitis E virus infection: A prospective, matched case-control study.

BACKGROUND: Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking. AIMS: To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population. METHODS: Swiss multicenter, prospective, observational, matched case-control study over 3 years (September 2019-October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti-HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real-time polymerase chain reaction (RT-PCR). RT-PCR was performed on sera to confirm IgM positivity. RESULTS: We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti-HEV IgM-positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = -0.25) was observed only between acute HEV infection and NA. CONCLUSION: This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy.

Electrodiagnostic subtyping in Guillain-Barré syndrome patients in the International Guillain-Barré Outcome Study.

BACKGROUND AND PURPOSE: Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. METHODS: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. RESULTS: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. CONCLUSIONS AND DISCUSSION: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.

Guillain-Barré syndrome with overlap between the finger drop variant and acute bulbar palsy: a case report.

BACKGROUND: Guillain-Barré syndrome (GBS) is a clinically heterogenous disease and encompasses several distinct clinical variants. Overlap between these variants can pose a diagnostic challenge. We report a case of finger drop variant and acute bulbar palsy overlap as an unusual manifestation of GBS. CASE PRESENTATION: An 81-year-old man presented with dysarthria, dysphagia, and upper limb weakness. Neurological examination revealed impaired tongue protrusion, the finger drop sign, and diminished brachioradial and triceps muscle reflexes. Nerve conduction studies showed reduced amplitudes and decreased velocities in the median and ulnar nerves. Cerebrospinal fluid analysis revealed albuminocytological dissociation and an anti-ganglioside antibody study revealed positivity for GM1, asialo-GM1, GT1a, GD1b, and GQ1b. As GBS was suspected, we initiated intravenous immunoglobulin treatment, resulting in gradual improvement within the next 3 weeks. CONCLUSION: To the best of our knowledge, this is the first reported case of an overlap between the finger drop variant and acute bulbar palsy in GBS, highlighting the importance of considering GBS when patients present with a combination of atypical symptoms. Anti-ganglioside antibodies can be helpful and add diagnostic value in these complex cases.

Guillain-Barre syndrome following scrub typhus: a case report and literature review.

BACKGROUND: Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi. Guillain-Barre syndrome (GBS) is an autoimmune-mediated peripheral neuropathy with a frequent history of prodromal infections, but GBS associated with scrub typhus is very rare. CASE PRESENTATION: We report a 51-year-old male patient who developed dysarthria and peripheral facial paralysis following the cure of scfrub typhus. CSF examination and electrophysiological findings suggested a diagnosis of GBS. After treatment with intravenous immunoglobulin, the patient's neurological condition improved rapidly. CONCLUSIONS: Scrub typhus infection is likely to be a potential predisposing factor in GBS, while scrub typhus-associated GBS has a favorable prognosis.

Relative frequencies and clinical features of Guillain-Barré Syndrome before and during the COVID-19 pandemic in North China.

OBJECTIVE: Most studies investigated the relationship between COVID-19 and Guillain-Barré syndrome (GBS) by comparing the incidence of GBS before and during the pandemic of COVID-19. However, the findings were inconsistent, probably owing to varying degrees of the lockdown policy. The quarantine requirements and travel restrictions in China were lifted around December 7, 2022. This study aimed to explore whether the relative frequency of GBS increased during the major outbreak in the absence of COVID-19-mandated social restrictions in China. METHODS: GBS patients admitted to the First Hospital, Shanxi Medical University, from December 7, 2022 to February 20, 2023, and from June, 2017 to August, 2019 were included. The relative frequencies of GBS in hospitalized patients during different periods were compared. The patients with and without SARS-CoV-2 infection within six weeks prior to GBS onset formed the COVID-GBS group and non-COVID-GBS group, respectively. RESULTS: The relative frequency of GBS among hospitalized patients during the major outbreak of COVID-19 (13/14,408) was significantly higher than that before the COVID-19 epidemic (29/160,669, P < 0.001). More COVID-GBS patients (11/13) presented AIDP subtype than non-COVID-GBS cases (10/27, P = 0.003). The mean interval between onset of infective symptoms and GBS was longer in COVID-GBS (21.54 ± 11.56 days) than in non-COVID-GBS (5.76 ± 3.18 days, P < 0.001). CONCLUSIONS: COVID-19 significantly increased the incidence of GBS. Most COVID-GBS patients fell into the category of AIDP, responded well to IVIg, and had a favorable prognosis.