Anti-sulfatide antibody associated GBS with headache and abdominal pain: a case report.

BACKGROUND: Guillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral nerves. Anti-sulfatide antibody-mediated complement is associated with acute sensorimotor peripheral neuropathy in GBS, which is characterized by pain and paresthesias. CASE PRESENTATION: The child was a 7-year-old girl with headache and abdominal pain, followed by limb numbness and pain. Cranial imaging showed ventricular dilatation, peripheral nerve function conduction examination showed polyradiculopathy, and cerebrospinal fluid tests showed normal cell counts but elevated protein levels, all of which led to the diagnosis of GBS. After treatment with intravenous immunoglobulin (400 mg/kg × 5 days), the symptoms did not improve, and muscle strength progressively worsened, accompanied by paroxysmal complexion flushing, heart rate fluctuation, hyperhidrosis, and a progressive increase in cerebrospinal fluid protein (up to 3780.1 mg/L). On the basis of these findings combined with serum anti-sulfatide IgM positivity, anti-sulfatide antibody-related GBS was considered, and treatment with low-dose prednisolone (1 mg/kg/d) led to symptom improvement. CONCLUSIONS: Anti-sulfatide antibody-associated GBS is associated with small fiber peripheral neuropathy. The main manifestations are pain, paresthesias and autonomic dysfunction. In addition to the dysfunction of spinal nerve root absorption caused by increased cerebrospinal fluid protein, autonomic dysfunction may be involved in pain. When the therapeutic effect of immunoglobulin is not satisfactory, a low dose and short course of corticosteroids can be considered, and the prognosis is good.

Guillain-Barr Syndrome Caused by Cytomegalovirus after Multiple Myeloma Treatment.

BACKGROUND: Both humoral and cell-mediated immunity of the patient affected by multiple myeloma (MM) are impaired; thus, infection is the main cause of the onset of symptoms and death caused by MM. Bortezomib is a first-line drug approved for patients with multiple myeloma (MM) and has significantly increased their overall survival. However, bortezomib-induced peripheral neuropathy (PN) remains a significant side effect that has led to its discontinuation in some patients. Guillain-Barre syndrome (GBS) is thought to be related to immune damage, and most patients have cytomegalovirus (CMV), Epstein-Barr virus (EBV), or mycoplasma infection before onset. Cases of GBS secondary to MM are rare. METHODS: We provide a case of GBS caused by cytomegalovirus infection after MM treatment, and briefly review the existing literature. RESULTS: Secondary GBS after MM. This patient received active treatment. The clinical symptoms are gradually improving. CONCLUSIONS: The use of bortezomib has the risk of reactivating the virus. It is more about the reactivation of hep-atitis B virus. Nonetheless, cytomegalovirus and Epstein-Barr virus shall have our attention. Patients with MM need to monitor CMV, regularly, especially during the treatment of bortezomib. At the same time, they also need to closely monitor the symptoms and signs of the nervous system to guard against the occurrence of GBS.

Concurrent transverse myelitis and acute inflammatory demyelinating polyneuropathy.

A woman in her 40s presented with thoracic banding dysaesthesia and lower motor neuron weakness. Spinal imaging revealed a short segment of transverse myelitis and neurophysiology was suggestive of concurrent acute inflammatory demyelinating polyneuropathy. The patient improved with consecutive intravenous immunoglobulin and methylprednisolone treatment. Acute inflammatory demyelinating polyneuropathy is a progressive immune-mediated peripheral neuropathy which responds to intravenous immunoglobulin or plasmapheresis, whereas transverse myelitis is a central inflammatory syndrome usually treated with corticosteroid. We highlight differentiating features of the clinical presentation and the utility of investigations such as neurophysiology and MRI along with a review of treatment and the role for corticosteroid therapy.

Triple Trouble.

We present a case of a 24-year-old female recently diagnosed with acute leukemia who came with complaints of fever for 14 days, progressive lower limb weakness, and multiple episodes of vomiting in the last 1 day. In nerve conduction studies, a diagnosis of Guillain-Barré syndrome (GBS) was established. Fever with thrombocytopenia workup revealed a positive dengue nonstructural protein 1 (NS1) and immunoglobulin M (IgM) report. Immunophenotyping confirmed pre-B acute lymphoblastic leukemia (ALL). As leukemia is an immunocompromised state, the peripheral nervous system vulnerability is increased, or infection could precipitate an immune neuropathy. About 10% of adult ALL presents with central nervous system (CNS) leukemias; a higher incidence is seen in mature B ALL. There is some evidence to suggest immunosuppression secondary to intensive chemotherapy (vincristine-induced dying back neuropathy), which was not started in our case. This rare combination in a short period of time with a worsening situation paralyzed the line of management. Few reports described GBS in patients with dengue in adults. The association of Guillan-Barre syndrome and ALL could be coincidental or has a pathophysiological basis and is under basic investigation.

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.

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.

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome.

BACKGROUND: Neurofilament light chain (NfL) is a biomarker for axonal damage in several neurological disorders. We studied the longitudinal changes in serum NfL in patients with Guillain-Barré syndrome (GBS) in relation to disease severity, electrophysiological subtype, treatment response, and prognosis. METHODS: We included patients with GBS who participated in a double-blind, randomised, placebo-controlled trial that evaluated the effects of a second course of intravenous immunoglobulin (IVIg) on clinical outcomes. Serum NfL levels were measured before initiation of treatment and at one, two, four, and twelve weeks using a Simoa HD-X Analyzer. Serum NfL dynamics were analysed using linear mixed-effects models. Logistic regression was employed to determine the associations of serum NfL with clinical outcome and the prognostic value of serum NfL after correcting for known prognostic markers included in the modified Erasmus GBS Outcome Score (mEGOS). FINDINGS: NfL levels were tested in serum from 281 patients. Serum NfL dynamics were associated with disease severity and electrophysiological subtype. Strong associations were found between high levels of serum NfL at two weeks and inability to walk unaided at four weeks (OR = 1.74, 95% CI = 1.27-2.45), and high serum NfL levels at four weeks and inability to walk unaided at 26 weeks (OR = 2.79, 95% CI = 1.72-4.90). Baseline serum NfL had the most significant prognostic value for ability to walk, independent of predictors included in the mEGOS. The time to regain ability to walk unaided was significantly longer for patients with highest serum NfL levels at baseline (p = 0.0048) and week 2 (p < 0.0001). No differences in serum NfL were observed between patients that received a second IVIg course vs. IVIg and placebo. INTERPRETATION: Serum NfL levels are associated with disease severity, axonal involvement, and poor outcome in GBS. Serum NfL potentially represents a biomarker to monitor neuronal damage in GBS and an intermediate endpoint to evaluate the effects of treatment. FUNDING: Prinses Beatrix Spierfonds W.OR19-24.

Guillain-Barré syndrome: immunopathogenesis and therapeutic targets.

INTRODUCTION: Guillain-Barré syndrome (GBS) is a group of acute immune-mediated disorders in the peripheral nervous system. Both infectious and noninfectious factors are associated with GBS, which may act as triggers of autoimmune responses leading to neural damage and dysfunction. AREAS COVERED: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines as well as flaviviruses have been associated with GBS, although a robust conclusion has yet to be reached. Immunomodulatory treatments, including intravenous immunoglobulins (IVIg) and plasma exchange (PE), have long been the first-line therapies for GBS. Depending on GBS subtype and severity at initial presentation, the efficacy of IVIg and PE can be variable. Several new therapies showing benefits to experimental animals merit further investigation before translation into clinical practice. We review the state-of-the-art knowledge on the immunopathogenesis of GBS in the context of coronavirus disease 2019 (COVID-19). Immunomodulatory therapies in GBS, including IVIg, PE, corticosteroids, and potential therapies, are summarized. EXPERT OPINION: The association with SARS-CoV-2 remains uncertain, with geographical differences that are difficult to explain. Evidence and guidelines are lacking for the decision-making of initiating immunomodulatory therapies in mildly affected patients or patients with regional subtypes of GBS.

Efgartigimod in the treatment of Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré Syndrome (GBS) is caused by immunoglobulin G (IgG) autoantibodies. Efgartigimod, a human IgG antibody Fc fragment that acts as a natural ligand for the FcRn, can increase IgG degradation, which thus may be a promising therapeutic drug for GBS. CASE PRESENTATION: The two patients presented with postinfectious and acute flaccid paralysis. On admission, they were bedridden. Nerve conduction studies indicated peripheral neuropathy. GBS was suspected and they are treated with two doses of efgartigimod (10 mg/kg) within 5 days. Their muscle strength improved gradually and 4 weeks after the initial dose, they could walk independently. Following the first dose, Patient 1 complaint of muscle soreness, which subsided the next morning. Patient 2 was intubated due to respiratory failure the day after the initial dose, and did not report other adverse effects. DISCUSSION: In GBS patients, two doses of efgartigimod (10 mg/kg) were effective in rapidly improving muscle strength, with a satisfactory safety profile. The findings suggest a potential role for efgartigimod in modifying the disease process in GBS patients. CONCLUSION: Efgartigimod seems effective and safe in the treatment of GBS. This study indicates the potential role of efgartigimod as a novel treatment option for GBS. Well-designed clinical trials should be conducted.

Acute sensorimotor paraneoplastic neuropathy in a patient with small cell prostate cancer.

The authors describe a patient with a background of metastatic small cell prostate cancer who presented with a rapidly evolving sensorimotor neuropathy with bulbar features closely resembling Guillain-Barré syndrome, with a good initial response to intravenous immunoglobulins and platinum-based chemotherapy. This represented a likely paraneoplastic manifestation of the patient's urological malignancy.

Reversible splenial lesion syndrome in patient with acute motor and sensory axonal neuropathy.

Even though the classical clinical concept supports the clear difference between diseases affecting the central and peripheral nervous systems, this difference is becoming less rigid. Here, we report the case of a 50-year-old male patient who presented with acroparaesthesia, headache, and flaccid tetraparesis after febrile diarrhea. Nerve conduction studies indicated action potentials with low amplitudes, which are typical in acute motor and sensory axonal neuropathy. Magnetic resonance revealed a round lesion in the splenium consistent with a diagnosis of reversible splenial lesion syndrome. A polyclonal antiganglioside antibody response was detected. The patient was successfully treated with intravenous immunoglobulins. The coexistence of reversible splenial lesion syndrome and acute motor and sensory axonal neuropathy has not been described in the literature so far. We discuss our diagnostic dilemmas and the possible role of antiganglioside antibodies in the occurrence of simultaneous lesions of the central and peripheral nervous systems.

Guillain-Barré syndrome following primary cytomegalovirus infection in a patient with liver transplantation.

We present the case of a man in his 60s with a 5-month medical history of deceased donor liver transplantation, who developed Guillain-Barré syndrome (GBS) secondary to a primary cytomegalovirus (CMV) infection. This was confirmed by molecular tests and serology antibodies that ruled out other frequent aetiologies. Therapy with intravenous immunoglobulin and valganciclovir was started and the patient gradually improved over the weeks. GBS is the most common aetiology of paralysis worldwide, and it is an autoimmune-mediated neuropathy that is frequently caused by a preceding infection. Few cases of GBS have been reported in the context of liver transplant recipients, and those related to CMV infection are extremely rare. This case highlights the importance of considering GBS as a possible differential diagnosis in patients with solid organ transplantation, and it contributes to the knowledge of other infrequent aetiologies of this condition.

[Prospect of novel therapies in immune-mediated neuropathies].

The efficacy of immunotherapies such as steroids, plasmapheresis, and intravenous immunoglobulin have been proven in various immune-mediated neuropathies. However, these treatments sometimes lack the efficacy in a part of patients with the immune-mediated neuropathies. In addition, anti-myelin associated glycoprotein (MAG) neuropathy is usually refractory to the treatments. Recently, novel therapies targeting a molecule which are associated with pathogenesis of immune-mediated diseases, have been developed. These molecularly targeted therapies are notable in immune-mediated neuropathies as novel drug candidates. In the present article, current treatments and future prospect of novel therapies in immune-mediated neuropathies will be reviewed.

Synergistic effects of immune checkpoints and checkpoint inhibitors in inflammatory neuropathies: Implications and mechanisms.

Immune checkpoint molecules play pivotal roles in the regulation of immune homeostasis. Disruption of the immune checkpoints causes autoimmune/inflammatory as well as malignant disorders. Over the past few years, the immune checkpoint molecules with inhibitory function emerged as potential therapeutic targets in oncological conditions. The inhibition of the function of these molecules by using immune checkpoint inhibitors (ICIs) has brought paradigmatic changes in cancer therapy due to their remarkable clinical benefits, not only in improving the quality of life but also in prolonging the survival time of cancer patients. Unfortunately, the ICIs soon turned out to be a "double-edged sword" as the use of ICIs caused multiple immune-related adverse effects (irAEs). The development of inflammatory neuropathies such as Guillain-Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) as the secondary effects of immunotherapy appeared very challenging as these conditions result in significant and often permanent disability. The underlying mechanism(s) through which ICIs trigger inflammatory neuropathies are currently not known. Compelling evidence suggests autoimmune reaction and/or inflammation as the independent risk mechanism of inflammatory neuropathies. There is a lack of understanding as to whether prior exposure to the risk factors of inflammatory neuropathies, the presence of germline genetic variants in immune function-related genes, genetic variations within immune checkpoint molecules, the existence of autoantibodies, and activated/memory T cells act as determining factors for ICI-induced inflammatory neuropathies. Herein, we highlight the available pieces of evidence, discuss the mechanistic basis, and propose a few testable hypotheses on inflammatory neuropathies as irAEs of immunotherapy.

Guillain-Barré Syndrome.

OBJECTIVE: This article summarizes the clinical features, diagnostic criteria, differential diagnosis, pathogenesis, and prognosis of Guillain-Barré syndrome (GBS), with insights into the current and future diagnostic and therapeutic interventions for this neuromuscular syndrome. LATEST DEVELOPMENTS: GBS is an acute, inflammatory, immune-mediated polyradiculoneuropathy that encompasses many clinical variants and divergent pathogenic mechanisms that lead to axonal, demyelinating, or mixed findings on electrodiagnostic studies. The type of antecedent infection, the development of pathogenic cross-reactive antibodies via molecular mimicry, and the location of the target gangliosides affect the subtype and severity of the illness. The data from the International GBS Outcome Study have highlighted regional variances, provided new and internationally validated prognosis tools that are beneficial for counseling, and introduced a platform for discussion of GBS-related open questions. New research has been undertaken, including research on novel diagnostic and therapeutic biomarkers, which may lead to new therapies. ESSENTIAL POINTS: GBS is among the most frequent life-threatening neuromuscular emergencies in the world. At least 20% of patients with GBS have a poor prognosis and significant residual deficits despite receiving available treatments. Research is ongoing to further understand the pathogenesis of the disorder, find new biomarkers, and develop more effective and specific treatments.

Guillain-Barré syndrome in patients dying with COVID-19 in Italy: a retrospective study.

INTRODUCTION: We presented a four-case series of COVID-19 related deaths occurred in patients with Guillain-Barré syndrome (GBS) between February 2020 and January 2022 in Italy. METHODS: They were extracted from 8,436 medical charts of COVID-19 patients dying. All cases, ranged 48-73 years, showed classical GBS clinical onset - limb weakness, sensory deficits, hypoareflexia - and three of them were admitted in intensive care unit (ICU) for ventilator support. RESULTS: The cerebrospinal fluid showing albumin-cytological dissociation was performed in two cases. Nerve conduction studies supported the diagnosis in all cases. Interstitial pneumonia was documented by chest X-rays or CT scans in all cases: they were treated with intravenous immunoglobulin (IVIg) and the drugs used for COVID-19 infection. CONCLUSIONS: Although the mechanism of GBS onset is still unclear in COVID-19, fatal cases may be more frequent than other virus-related GBS, so that strictly monitoring in high-risk patients could dramatically decrease the mortality of GBS.

Guillain-Barré syndrome as clinical presentation of a recently acquired hepatitis C.

About 40% of the Guillain-Barré syndrome (GBS) cases are associated with prodromal infections; occasionally, it has been associated to chronic hepatitis C or its reactivation. A 38-year-old man came to our attention after transaminase elevation occurred during recovery from GBS. All the possible causes of acute hepatitis were excluded except for the positivity of HCVRNA, and a diagnosis of new onset hepatitis C was made. Recalling patient history, we observed that (i) anti-HCV antibodies were negative and liver enzymes were normal 7 weeks before GBS onset; (ii) in the early stages of ICU admission, liver enzymes started to rise, but the elevation remained mild under steroid treatment; (iii) serum aminotransferase peak occurred 11 weeks after GBS onset; and (iv) HCV RNA was already significantly high when anti-HCV antibodies became positive, consistent with an acute hepatitis. Furthermore, anti-HCV seroconversion was likely delayed or blurred by steroids and immunoglobulin infusions. The interval of time between GBS onset and transaminase elevation compared with the patient clinical history allows us to establish a cause-effect relationship between the two diseases. All patients with GBS should be tested for hepatitis C, or its reactivation if already present, and followed up for an early diagnosis and treatment.

[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.

An exploratory international survey of the assessments and interventions used by occupational therapists and physiotherapists during the hospitalization of people with Guillain-Barré syndrome.

Guillain-Barré syndrome is a rare neurological condition. Although some people make a substantial functional recovery, almost half require intensive rehabilitation. Data were collected using a cross-sectional survey which investigated the assessments and interventions used by occupational therapists and physiotherapists for people with Guillain-Barré syndrome. Seventy valid responses were received from 10 countries. The survey highlighted four factors about current practice: (i) practitioners did not identify the use of formal clinical guidelines or protocols for Guillain-Barré Syndrome treatment of the upper limb; (ii) a range of standardized and non-standardized assessment and goal-setting tools are utilized; (iii) interventions include passive and active range of motion exercises, and the prescription of upper limb/hand splints; and (iv) interdisciplinary practice is common in the intensive care unit and during acute phases of Guillain-Barré syndrome, whereas discipline-specific work is more common during rehabilitation. A range of goal-setting and assessment tools are used by occupational therapists and physiotherapists during the hospitalization of people with Guillain-Barré syndrome. The type and duration of interventions vary and may reflect the lack of international protocols for Guillain-Barré syndrome rehabilitation.