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.

Increased risk of depression after Guillain-Barré syndrome.

INTRODUCTION/AIMS: Guillain-Barré syndrome (GBS) is a potentially life-threatening disorder, and some patients may develop subsequent depression related to traumatic stress or permanent loss of motor function. We determined the short-term (0 to 2 years) and long-term (>2 years) risk of depression after GBS. METHODS: Individual-level data from nationwide registries were linked in this population-based cohort study of all first-time hospital-diagnosed GBS patients in Denmark between 2005 and 2016 and individuals from the general population. After exclusion of individuals with previous depression, we computed cumulative rates of depression, defined as either antidepressant drug prescription or depression hospital diagnosis. We used Cox regression analyses to calculate adjusted depression hazard ratios (HRs) after GBS. RESULTS: We identified 853 incident GBS patients and recruited 8639 individuals from the general population. Depression within 2 years was observed in 21.3% (95% confidence interval [CI], 18.2% to 25.0%) of GBS patients and in 3.3% (95% CI, 2.9% to 3.7%) of those in the general population, resulting in a HR of 7.6 (95% CI, 6.2 to 9.3). The highest depression HR was observed within the first 3 months after GBS (HR, 20.5; 95% CI, 13.6 to 30.9). After the first 2 years, GBS patients and the general population members had similar long-term depression risks with an HR of 0.8 (95% CI, 0.6 to 1.2). DISCUSSION: During the first 2 years after GBS hospital admission, patients with GBS had a 7.6-fold increased hazard of depression compared with individuals in the general population. Two years after GBS, the risk of depression was similar to that of the background population.

Recombinant protein subunit COVID-19 vaccine-induced Guillain-Barré Syndrome in an adolescent: A case report.

Guillain-Barré Syndrome (GBS), an autoimmune neurological disease of peripheral nerves, has been causally associated with COVID-19 vaccination in adults. However, no such report has been published so far in children. We describe a 13-year-old female child who presented to the emergency department with complaints of bilateral upper limb, lower limb and truncal weakness over 3 days following first dose of recombinant protein subunit COVID-19 vaccine (Corbevax). Clinical examination and nerve conduction studies showed pure motor axonal polyneuropathy with absent compound muscle action potential (CMAP) in all sampled nerves of upper and lower limbs which was consistent with the diagnosis of GBS after ruling out possible alternative aetiologies. A temporal association between first dose of protein subunit COVID-19 vaccine administered a day prior and symptom onset was noted. The causality assessment using the World Health Organization (WHO) tool for adverse event following immunization (AEFI) assessment indicated vaccine product-related reaction categorized as A1. The patient's clinical condition improved after seven sessions of plasmapheresis. The purpose of this report is to create awareness among health care professionals about COVID-19 vaccine-induced GBS in children as early diagnosis and management can be critical in avoiding complications and improving patient outcomes.

Nodal-paranodal antibodies in HIV-immune mediated radiculo-neuropathies: Clinical phenotypes and relevance.

BACKGROUND: The frequency of nodal-paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described. METHODS: HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for immunoglobulin G (IgG) antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein(Caspr1)) cell adhesion molecules, using a live, cell-based assay. To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury. RESULTS: Twenty-four HIV-infected patients with IMRN were included in the study, 15 with chronic inflammatory demyelinating polyneuropathy (CIDP), 4 with ventral root radiculopathies (VRR), and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination (CCPD). Three patients (12.7%) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive, and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis, respectively. CONCLUSION: The frequency of nodal-paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.

Prognostic Implications of Early Albuminocytological Dissociation in Guillain-Barré Syndrome.

BACKGROUND: Half of Guillain-Barré syndrome (GBS) present elevated cerebrospinal fluid (CSF) protein levels within 1 week since symptom onset and 80% within 2 weeks. Our objective was to determine the clinical and prognostic implication of albuminocytological dissociation in early GBS. METHODS: An ambispective cohort study was conducted. Good outcome was considered if the patient was able to walk unaided (Guillain-Barré disability score [GDS] ≤ 2 points) at 3-month follow-up. Patients were classified into two groups: with and without albuminocytological dissociation; we compared clinical and paraclinic characteristics between the groups. We analyzed clinical and electrophysiological factors related to presenting early dissociation through a multivariate model. RESULTS: We included 240 patients who fulfilled Asbury criteria for GBS. On further selection, only 94 patients fulfilled inclusion. Mean age was 45.94 ± 17.1 years and 67% were male. Median time from symptom onset to admission was 5 days (IQR 3-6). Regarding albuminocytological dissociation and electrophysiological variants, we found a significant difference: acute inflammatory demyelinating polyneuropathy (AIDP) [60.6% vs 26.2%, p = 0.002], acute motor axonal neuropathy (AMAN) [21.2% vs 49.1%, p = 0.009] and acute motor sensory axonal neuropathy (AMSAN) [12.1% vs 1.6%, p = 0.05]. We did not observe significant differences in recovery of independent walking in short term between both groups. The presence of conduction block in any variant (OR 3.21, 95% CI 1.12-9.16, p = 0.02) and absence of sural registration (OR 5.69, 95% CI 1.48-21.83, p = 0.011) were independent factors related to early dissociation. CONCLUSIONS: Early dissociation (<7 days) is not associated with any particular clinical feature or unfavorable outcome. It is more common to see in AIDP rather than axonal variants.

Outcome of Guillain-Barré syndrome following intravenous immunoglobulin compared to natural course.

BACKGROUND AND PURPOSE: Intravenous immunoglobulin (IVIg) is recommended in Guillain-Barré syndrome (GBS), but its efficacy may vary in different subtypes. We report the outcomes of patients with GBS following IVIg treatment compared to the natural course (NC). We also compare the effect of IVIg treatment in different subtypes of GBS. METHODS: From a cohort of 528 GBS subjects, we have extracted 189 patients who received IVIg and compared their outcomes with 199 age- and peak disability-matched patients who did not receive IVIg, plasmapheresis, or corticosteroid. Disability was assessed using the 0-6 Guillain-Barré Syndrome Disability Scale (GBSDS). Clinical and neurophysiological subtypes were recorded. The primary outcome was functional disability at 6 months, which was categorized as complete (GBSDS ≤ 1), partial (GBSDS 2-3), or poor (GBSDS > 3). The secondary outcomes were in-hospital death, duration of hospitalization, and mechanical ventilation. RESULTS: In-hospital death (2.6% vs. 2%, p = 0.74) and 3-month poor recovery (20.7% vs. 18%) were similar in the IVIg and NC groups. At 6 months, however, a lesser proportion of patients in the IVIg group had poor recovery (2.2% vs. 8.3%, p = 0.026). The outcomes of IVIg and NC were compared in 72 acute motor axonal neuropathy (AMAN) and 256 acute inflammatory demyelinating polyradiculoneuropathy (AIDP) patients. IVIg therapy did not alter the outcome in AMAN but resulted in a lesser proportion of poor recovery at 6 months in AIDP (0.8% vs. 6.6%, p = 0.03). CONCLUSIONS: IVIg is beneficial in AIDP variants of GBS but not in the AMAN subtype. A customized treatment may be cost-effective until a randomized controlled trial is conducted in AMAN.

Changes in motor nerve excitability in acute phase Guillain-Barré syndrome.

BACKGROUND: The most common subtypes of Guillain-Barré syndrome (GBS) are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In the first days after the onset of weakness, standard nerve conduction studies (NCS) may not distinguish GBS subtypes. Reduced nerve excitability may be an early symptom of nerve dysfunction, which can be determined with the compound muscle action potential (CMAP) scan. The aim of this study was to explore whether early changes in motor nerve excitability in GBS patients are related to various subtypes. METHODS: Prospective case-control study in 19 GBS patients from The Netherlands and 22 from Bangladesh. CMAP scans were performed within 2 days of hospital admission and NCS 7-14 days after onset of weakness. CMAP scans were also performed in age- and country-matched controls. RESULTS: CMAP scan patterns of patients who were classified as AMAN were distinctly different compared to the CMAP scan patterns of the patients who were classified as AIDP. The most pronounced differences were found in the stimulus intensity parameters. CONCLUSIONS: CMAP scans made at hospital admission demonstrate several characteristics that can be used as an early indicator of GBS subtype.

Is Guillain-Barrè syndrome triggered by SARS-CoV-2? Case report and literature review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent responsible for coronavirus disease 2019 (COVID-19). Respiratory and gastrointestinal manifestations of SARS-CoV-2 are well described, less defined is the clinical neurological spectrum of COVID-19. We reported a case of COVID-19 patient with acute monophasic Guillain-Barré syndrome (GBS), and a literature review on the SARS-CoV-2 and GBS etiological correlation. CASE DESCRIPTION: A 68 years-old man presented to the emergency department with symptoms of acute progressive symmetric ascending flaccid tetraparesis. Oropharyngeal swab for SARS-CoV-2 tested positive. Neurological examination showed bifacial nerve palsy and distal muscular weakness of lower limbs. The cerebrospinal fluid assessment showed an albuminocytologic dissociation. Electrophysiological studies showed delayed distal latencies and absent F waves in early course. A diagnosis of Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP) subtype of GBS was then made. CONCLUSIONS: Neurological manifestations of COVID-19 are still under study. The case we described of GBS in COVID-19 patient adds to those already reported in the literature, in support of SARS-CoV-2 triggers GBS. COVID-19 associated neurological clinic should probably be seen not as a corollary of classic respiratory and gastrointestinal symptoms, but as SARS-CoV-2-related standalone clinical entities. To date, it is essential for all Specialists, clinicians and surgeons, to direct attention towards the study of this virus, to better clarify the spectrum of its neurological manifestations.

Abnormal expression of NF-κB-related transcripts in blood of patients with inflammatory peripheral nerve disorders.

The NF-κB family includes some transcription factors which have important functions in the regulation of immune responses, therefore participating in the pathophysiology of inflammatory conditions such as peripheral neuropathies. We have quantified expression of a number of NF-κB-related transcripts in patients with Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) versus healthy subjects. These transcripts have been previously shown to be functionally related with this family of transcription factors. Expressions of ATG5, DICER-AS1, PACER, DILC, NKILA and ADINR have been increased in both CIDP and GBS patients compared with controls. However, expression of ATG5 was not different between female CIDP cases and female controls. Moreover, expression of PACER was not different between male GBS cases and male controls. Expression levels of CHAST and CEBPA were not different between patients and controls. Expression of none of the assessed genes was different between GBS and CIDP cases. Significant correlations have been revealed between expression amounts of NF-κB-related transcripts both among CIDP/ GBS patients and among controls except for NKILA/ATG5, ADINR/ATG5 and PACER/ATG5 and DICER-AS1/ATG5 pairs among controls whose expression levels have not been correlated. In the patient group, CEBPA/PACER, CHAST/PACER and CHAST/DICER-AS1 pairs had the most robust correlations (r = 0.94). Among controls, NKILA/ADINR pair had the most strong correlation (r = 0.78). ADINR and DICER-AS1 levels could differentiate CIDP cases from controls with 100% sensitivity and specificity. In differentiation of GBS cases from controls, these two transcripts had the AUC values of 0.99 and 1. Combination transcript levels of NF-κB-related transcripts similarly detects CIDP and GBS cases from healthy controls with 100% sensitivity and specificity. Therefore, NF-κB-related transcripts are possibly involved in the pathophysiology of inflammatory peripheral nerve disorders and can be used as diagnostic markers for these conditions.

A 50-Year-Old Patient with Guillain-Barré Syndrome after COVID-19: A Case Report.

Severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, causes acute respiratory disease (coronavirus disease 2019; COVID-19). However, the involvement of other mechanisms is also possible, and neurological complications are being diagnosed more frequently. Here, we would like to present a case of a Polish patient with Guillain-Barré syndrome (GBS), after a documented history of COVID-19: A 50-year-old man, 18 days after the onset of COVID-19 symptoms, had progressive quadriparesis preceded by 1-day sensory disturbances. Based on the clinical picture, the results of diagnostic work-up including a nerve conduction study (ENG) that revealed a demyelinating and axonal sensorimotor polyneuropathy, and cerebrospinal fluid (CSF) analysis that showed albumin-cytological dissociation, an acute inflammatory demyelinating polyneuropathy was confirmed, consistent with GBS. Upon a therapeutic plasma exchange (TPE), the patient's condition improved. The presented case of GBS in a patient after mild COVID-19 is the first case in Poland that has supplemented those already described in the global literature. Attention should be drawn to the possibility of GBS occurring after SARS-CoV-2 infection, even when it has a mild course.

Clinical features of Guillain-Barré syndrome patients with elevated serum creatine kinase levels.

BACKGROUND: It is not well defined whether Guillain-Barré syndrome (GBS) patients with elevated serum creatine kinase (CK) levels have characteristic clinical features and are related to the subgroups of GBS. METHODS: We retrospectively studied 51 consecutive patients with GBS, who visited our hospital, and compared clinical, laboratory and electrophysiological findings between patients with and without elevated CK levels. RESULTS: Of 51 patients, 14 patients (27%) showed an elevation of serum CK levels. When compared with patients with the normal CK levels, the ratios of male, antecedent infections, and anti-GM1 antibody positivity were significantly higher in patients with elevated CK levels. The ratios of hypoesthesia, cranial nerve involvement, and urinary retention were significantly less in patients with elevated CK levels. There were no significant differences in disability at peak between two groups. In the electrophysiological examination, sensory nerve abnormalities were not observed. Although some patients with elevated CK levels showed prolongation of distal motor latencies (DMLs) and increase of durations in the initial examination, development of the prolongation of DMLs and increase of durations was not observed in the follow-up examinations. The findings were consistent with acute motor axonal neuropathy (AMAN) with reversible conduction failure (RCF) but not acute inflammatory demyelinating polyneuropathy (AIDP). CONCLUSIONS: The results suggest that the GBS patients with elevated CK levels represent not a group of AIDP but a group of AMAN with axonal degeneration or RCF even though the initial electrophysiological examination shows AIDP pattern.

Increased incidence of axonal Guillain-Barré syndrome in La Spezia area of Italy: A 13-year follow-up study.

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy with a worldwide incidence of 0.81-1.89 per 100 000 person-years. In Europe and North America only 5% of patients with GBS have axonal subtypes, which in South America and Asia account for 30%-47% of cases. The aim of our study is to assess the annual incidence and clinical features of GBS in La Spezia area in Italy. A retrospective (from 1 January 2003 to 31 December 2011) followed by a prospective (from 1 January 2012 to 31 December 2015) analysis was carried out on patients admitted to La Spezia hospital who fulfilled the GBS diagnostic criteria. A total of 86 patients (58 men), mean age of 62.7 years (range 21-90), were included. The mean annual incidence rate was 3/100 000 (range: 0.9/100 000-5.37/100 000) significantly higher than the European incidence (P < 0.001). Forty-seven percent were classified as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 35% as acute motor and motor-sensory axonal neuropathy (AMAN-AMSAN), 13% as variant forms, and 5% were not defined. AIDP was most common in "Golfo dei Poeti" (50%) and "Val di Magra" (63.2%), whereas AMAN/AMSAN prevailed in "Val di Vara" (63.6%) and "Riviera Spezzina" (62.5%) (P = 0.024). In La Spezia area GBS incidence (especially the AMAN subtype) is significantly higher than the incidence reported in Europe. AIDP predominates in the eastern area whereas AMAN/AMSAN in the western, with a significantly different incidence rate (P = 0.003). Prospective studies to assess possible predisposing environmental factors are needed.

Neurologic Immune-Related Adverse Events Associated with Immune Checkpoint Inhibition.

PURPOSE OF REVIEW: This review highlights the spectrum of neurologic adverse events seen with use of immune checkpoint inhibitors (ICIs), their potential mechanisms, the treatments undertaken, and the clinical outcomes. RECENT FINDINGS: The advent of ICIs has revolutionized cancer therapy. Neurologic adverse events (NAEs) are rare but clinically significant complication of ICIs. They can involve both the central and peripheral nervous system. Examples include myositis, neuropathy, encephalopathy, and myasthenia gravis. Treatment consists of holding the ICI, administration of corticosteroids, and other immunomodulatory agents as needed. The outcomes are generally favorable; however, rarely severe events can lead to significant morbidity and even mortality. Identifying and treating the range of neurologic adverse events that may potentially arise with ICIs is very important as the oncologic indications for their use continues to expand.

Prospective comparison of acute motor axonal neuropathy and acute inflammatory demyelinating polyradiculoneuropathy in 140 children with Guillain-Barré syndrome in India.

INTRODUCTION: There have been few reports on subtypes of Guillain-Barré syndrome (GBS) in children. We compared clinical and laboratory findings of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). METHODS: One hundred forty children with GBS were included. Based on nerve conduction study (NCS) findings, patients were subclassified as AIDP, AMAN, acute motor sensory axonal neuropathy (AMSAN), and equivocal. RESULTS: Clinically, 72.1% of patients had pure motor, 24.3% motor sensory, and 3.4% Miller Fisher syndrome. Based on NCS, 67.8% of patients had AIDP, 23.6% had AMAN, and 4.3% had AMSAN. By 3 months, 2.1% patients had died, 47.1% had complete recovery, and 24.3% had poor recovery (wheelchair-bound). Children with AMAN had more frequent lower limb weakness (P = 0.02) and a lower probability of complete recovery (P = 0.01) at 3 months than children with AIDP (56% vs. 30%). DISCUSSION: AIDP is the most common GBS subtype in children. It is characterized by better recovery at 3 months when compared with AMAN. Muscle Nerve 57: 761-765, 2018.

Differences between acute-onset chronic inflammatory demyelinating polyneuropathy and acute inflammatory demyelinating polyneuropathy in adult patients.

Acute inflammatory demyelinating polyneuropathy (AIDP) and acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) are conditions presenting overlapping clinical features during early stages (first 4 weeks), although the latter may progress after 8 weeks. The aim of this study was to identify predictive factors contributing to their differential diagnosis. Clinical records of adult patients with AIDP or A-CIDP diagnosed at our institution between January 2006 and July 2017 were retrospectively reviewed. Demographic characteristics, clinical manifestations, cerebrospinal-fluid (CSF) findings, treatment and clinical evolution were analyzed. Nerve conduction studies were performed in all patients with at least 12 months follow-up. A total of 91 patients were included (AIDP, n = 77; A-CIDP, n = 14). The median age was 55.5 years in patients with A-CIDP vs 43 years in AIDP (P = .07). The history of diabetes mellitus was more frequent in A-CIDP (29% vs 8%, P = .04). No significant differences between groups were observed with respect to: human immunodeficiency virus (HIV) status, presence of auto-immune disorder or oncologic disease. Cranial, motor and autonomic nerve involvement rates were similar in both groups. Patients in the A-CIDP group showed higher frequency of proprioceptive disturbances (83% vs 28%; P < .001), sensory ataxia (46% vs 16%; P = .01), and the use of combined immunotherapy with corticoids (29% vs 3%; P = .005). There were no significant differences in CSF findings, intensive care unit (ICU) admission, or mortality rates. During the first 8 weeks both entities are practically indistinguishable. Alterations in proprioception could suggest A-CIDP. Searching for markers that allow early differentiation could favor the onset of corticotherapy without delay.

Early electrophysiological findings in acute inflammatory demyelinating polyradiculoneuropathy variant of Guillain-Barre syndrome in the Pakistani population - a comparison with global data.

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy are the most common variants of Guillian-Barre syndrome documented in the Asian population. However, the variability of early neurophysiologic findings in the Asian population compared to western data has not been documented. Eighty-seven cases of AIDP were retrospectively reviewed for their demographic, clinical, electrophysiological, and laboratory data. Mean age of subjects was 31 ± 8 years with males more commonly affected. Motor symptoms (97%) at presentation predominated. Common early nerve conduction findings included low motor amplitudes (85%), recordable sural sensory responses (85%), and absent H-reflex responses (65%). Prolonged F-latencies were found most commonly in posterior tibial nerves (23%) in the lower limbs and median and ulnar nerves (18%) in the upper limbs. Blink reflex (BR) studies were performed in 57 patients and were abnormal in 80% of those with clinical facial weakness and in 17 of 52 patients (33%) with no clinical cranial nerve signs, suggesting subclinical cranial nerve involvement. Abnormal motor and sensory amplitudes are seen early. Prolonged distal latencies, temporal dispersion/conduction blocks and sural sparing pattern are other common early nerve conduction study findings of AIDP seen in the Pakistani population. There are no significant differences in abnormalities of conduction velocities and delayed reflex responses compared to published data. The BR can help in the early diagnosis of AIDP.

Respiratory Muscle Assessment in Acute Guillain-Barré Syndrome.

PURPOSE: Guillain-Barré Syndrome (GBS) is a life-threatening disease due to respiratory muscle involvement. This study aimed at objectively assessing the course of respiratory muscle function in GBS subjects within the first week of admission to an intensive care unit. METHODS: Medical Research Council Sum Score (MRC-SS), vigorimetry, spirometry, and respiratory muscle function tests (inspiratory/expiratory muscle strength: PImax/PEmax, sniff nasal pressure: SnPna) were assessed twice daily. GBS Disability Score (GBS-DS) was assessed once daily. On days one (d1) and seven (d7), blood gases and twitch mouth pressure during magnetic phrenic nerve stimulation (Pmo,tw) were additionally evaluated. RESULTS: Nine subjects were included. MRC-SS, vigorimetry, PImax, and SnPna increased between d1 and d7. GBS-DS, spirometry and Pmo,tw remained unaltered. Only SnPna correlated closely with the MRC-SS on both d1 (r = 0.77, p = 0.02) and d7 (r = 0.74, p = 0.02). CONCLUSION: SnPna was the only parameter that correlated with MRC-SS, while the current gold standard of spirometry measurement did not.