Polycranial neuropathy and sensory ataxia with IgG anti-GD1a antibody as a variant of Guillain–Barré syndrome

Immunoglobulin G (IgG) anti-GD1a ganglioside antibody is an important marker of Guillain–Barré syndrome (GBS). This antibody is highly associated with disease severity, the need for mechanical ventilation, and axonal degeneration of peripheral nerves. We report a 46-year-old female patient manifesting the IgG anti-GD1a antibody with polycranial neuropathy and sensory ataxia as a variant of GBS. She presented with slurred speech, swallowing difficulties, and gait disturbance following diarrhea. Decreased sensations of vibration and position were found in her distal limbs and she had an ataxic gait with a positive Romberg sign. Her serum was positive for IgG anti-GD1a ganglioside antibody (1:640). Her neurological examination at the third month after intravenous Ig treatment showed complete recovery.     

The role of cytokines in Guillain–Barré syndrome

Cytokines play an important role in the pathogenesis of autoimmune diseases including Guillain–Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN). In this article, we reviewed the current knowledge of the role of cytokines such as TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-17, IL-10, IL-4 and chemokines in GBS and EAN as unraveled by studies both in the clinic and the laboratory. However, these studies occasionally yield conflicting results, highlighting the complex role that cytokines play in the disease process. Efforts to modulate cytokine function in GBS and other autoimmune disease have shown efficiency indicating that cytokines are important therapeutic targets.     

An electrophysiological classification associated with Guillain–Barré syndrome outcomes

Guillain–Barré syndrome (GBS) is an acute, post-infectious, inflammatory, autoimmune peripheral neuropathy with a highly diverse clinical course and outcome. We classified GBS on the basis of patients’ first nerve conduction and validated this system to be associated with outcome on the basis of electrophysiological characteristics during the acute phase of GBS. We retrospectively evaluated 40 GBS patients who underwent their first electrophysiological study within 14 days of onset and classified GBS into four patterns: (1) acute inflammatory demyelinating polyneuropathy (AIDP) pattern with sensory nerve conduction abnormalities (motor–sensory AIDP: MS-AIDP), (2) AIDP pattern without sensory nerve conduction abnormalities (motor AIDP: M-AIDP), (3) acute motor axonal neuropathy (AMAN) pattern, and (4) minor abnormalities pattern. We compared the clinical, electrophysiological, and laboratory findings between groups and determined subgroups associated with poor outcome. The MS-AIDP and AMAN patterns more frequently exhibited prolonged recovery compared with the M-AIDP and minor abnormalities patterns and were associated with prolonged recovery (specificity, 100 %; sensitivity, 73 %; P < 0.001). The period of inability to walk independently was significantly longer in the MS-AIDP and AMAN patterns than in the M-AIDP and minor abnormalities patterns (median 85 vs. 10 days; P < 0.001). In conclusion, our classification of GBS using a single nerve conduction study in the early phase of disease is associated with outcomes. This classification can be used to counsel individual patients and guide decision-making with respect to treatment.     

Intravenous immunoglobulin therapy for Guillain-Barré syndrome with IgG anti-GM1 antibody

To compare the effects of intravenous immunoglobulin (IVIg) therapy and plasmapheresis for the IgG anti-GM1-positive subtype of Guillain-Barré syndrome (GBS), clinical and electrophysiological recoveries were analyzed in 24 patients treated with IVIg (n = 10) or plasmapheresis (n = 14). At entry, there were no significant differences between the two patient groups in age, sex, clinical severity (Hughes grade), sum scores of distally evoked amplitudes of compound muscle action potentials (CMAPs), and frequency of Campylobacter jejuni infection. The patients treated with IVIg had significantly lower Hughes grade scores 1, 3, and 6 months after onset (P = 0.03), and a higher probability to regain independent locomotion at 6 months [P(logrank) = 0.044]. In the IVIg group, markedly rapid recovery (improvement by two or more Hughes grade scores within 4 weeks) was more frequent (6 of 10 vs. 3 of 14, P = 0. 03), and delayed recovery (unable to walk independently at 6 months) was less frequent (0 of 10 vs. 4 of 14, P = 0.06). CMAP sum score at 6 months tended to be greater for the IVIg group (P = 0.07). For the IgG anti-GM1-positive subgroup of GBS patients, IVIg therapy may be a more efficacious treatment than plasmapheresis.     

Axonal variants of Guillain–Barré syndrome: an update

Journal of Neurology - Axonal variants of Guillain–Barré syndrome (GBS) mainly include acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and...     

Can Subdural Hematoma Be a Trigger for Guillain–Barré Syndrome?

Guillain–Barré syndrome (GBS) is an acute inflammatory polyneuropathy which follows a precipitating event in approximately two thirds of cases. Although its pathogenesis is unclear, it is likely to be a consequence of an immune-mediated process. In the literature there are three case reports of GBS following subarachnoid hemorrhage, subdural hematoma, and facial bone fracture after head trauma.The unique feature of our case with GBS after subdural hematoma is the presence of cerebellar symptoms. We believe that GBS results from an aberrant immune response following trauma that somehow mistakenly attacks the nerve tissue of its host, and we discuss the effects of the trauma of head injury on cellular and humoral immunities and the absence of antiganglioside antibody (anti-GD1b IgG, which is accused of ataxia and cerebellar symptoms) in this case report.     

Preceding infections and anti-ganglioside antibody profiles assessed by a dot immunoassay in 306 French Guillain–Barré syndrome patients

We describe by an in-house dot immunoassay, specific anti-ganglioside and sulfatide antibodies, by comparing the results from a large group of 134 infected French GBS patients and those from 172 noninfected French GBS and 142 control groups. A recent infection was identified in 134/306 (43.8%) GBS patients: Campylobacter jejuni (24.6%) was the most common agent, followed by cytomegalovirus (12.4%), Mycoplasma pneumoniae (3.2%) and Epstein-Barr virus (1.3%). Anti-ganglioside antibodies were detected in 97/306 (31.7%) of total GBS patients, 82/134 (61.2%) of GBS patients with a recent identified infection and 15/172 (8.7%) of the patients without identified infection. According to the specificities and antibody classes, four specific IgG antibody profiles were individualised against the two major GM1 and GD1a gangliosides in motor axonal C. jejuni-associated GBS variants, against GQ1b and disialylated gangliosides in Miller Fisher syndrome and its variants. One specific IgM profile against GM2 was found in 16/38 (42%) of severe sensory demyelinating CMV-associated GBS and in 8/17 (47%) of subjects with recent CMV infection with no neurological disease. IgG or IgM antibodies to GM1 were found in 5/10 M. pneumoniae-infected patients. IgM antibodies to GM1 were observed in the control groups, 15% of the 74 patients with amyotrophic lateral sclerosis, 19% of the 51 patients with chronic inflammatory demyelinating polyneuropathy, and 9% of the 21 healthy control subjects. The fine specificity of the four IgG antibody profiles and the IgM anti-GM2 profile is closely related to the nature of the preceding infections and the pattern of clinical features.     

Guillain–Barré syndrome associated with normal or exaggerated tendon reflexes

Areflexia is part one of the clinical criteria required to make a diagnosis of Guillain-Barré syndrome (GBS). The diagnostic criteria were stringently developed to exclude non-GBS cases but there have been reports of patients with GBS following Campylobacter jejuni enteritis with normal and exaggerated deep tendon reflexes (DTRs). The aim of this study is to expand the existing diagnostic criteria to preserved DTRs. From the cohort of patients referred for anti-ganglioside antibody testing from hospitals throughout Japan, 48 GBS patients presented with preserved DTR at admission. Thirty-two patients had normal or exaggerated DTR throughout the course of illness whereas in 16 patients the DTR became absent or diminished during the course of the illness. IgG antibodies against GM1, GM1b, GD1a, or GalNAc-GD1a were frequently present in either group (84 vs. 94%), suggesting a close relationship between the two groups. We then investigated the clinical and laboratory findings of 213 GBS patients from three hospital cohorts. In 23 patients, eight presented with normal tendon reflexes throughout the clinical course of the illness. Twelve showed hyperreflexia, with at least one of the jerks experienced even at nadir, and exaggerated reflexes returning to normal at recovery. The other three had hyperreflexia throughout the disease course. Compared to 190 GBS patients with reduced or absent DTR, the 23 DTR-preserved patients more frequently presented with pure motor limb weakness (87 vs. 47%, p?=?0.00026), could walk 5?m independently at the nadir (70 vs. 33%, p?=?0.0012), more frequently had antibodies against GM1, GM1b, GD1a, or GalNAc-GD1a (74 vs. 47%, p?=?0.014) and were more commonly diagnosed with acute motor axonal neuropathy (65 vs. 34%, p?=?0.0075) than with acute inflammatory demyelinating polyneuropathy (13 vs. 43%, p?=?0.0011). This study demonstrated that DTRs could be normal or hyperexcitable during the entire clinical course in approximately 10% of GBS patients. This possibility should be added in the diagnostic criteria for GBS to avoid delays in diagnosis and effective treatment to these patients.     

Contact heat-evoked potentials as a useful means in patients with Guillain–Barré syndrome

Few objective methods have been utilized to identify the small myelinated fiber impairment causing neuropathic pain in Guillain–Barré syndrome (GBS). In this study, contact heat-evoked potentials (CHEPs) were applied to study the nociceptive pathway in GBS. Sixty GBS patients and fifty healthy controls were enrolled. The 60 GBS patients were divided into two subgroups presenting with or without subjective lower limb paresthesia (21/39). CHEPs were recorded at Cz and Pz with a peak thermal stimuli of 47 °C applied to the skin of the leg above the internal malleolus (AIM) and of the waist at the anterior superior iliac spine (ASIS) level. The N2 latency and N2–P2 amplitude of CHEPs were compared. When the skin of the leg AIM was stimulated, the N2 latency was significantly postponed (425.23 ± 28.66 vs. 402.30 ± 19.48 ms, P < 0.05) and the N2–P2 amplitude significantly decreased in GBS patients as compared to controls (32.71 ± 7.49 vs. 42.77 ± 8.71 μV, P < 0.05). Slower nerve conduction velocity was observed in GBS patients (11.84 ± 1.45 vs. 13.28 ± 0.66 ms, P < 0.05). However, no differences in N2 latency or N2–P2 amplitude were detected between the two subgroups of GBS patients with or without subjective lower limb paresthesia (P all >0.05). Moreover, there were no differences in N2 latency and N2–P2 amplitude among different groups when the waist was stimulated at the ASIS level. Our study suggested that CHEPs could be utilized as an objective and non-invasive tool to detect small myelinated fiber damage in GBS patients, especially for those without subjective paresthesia.     

Clinical and electrophysiological features of Guillain–Barré syndrome in Iran

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

An antibody to the GM1/GalNAc-GD1a complex correlates with development of pure motor Guillain–Barré syndrome with reversible conduction failure

Antibodies to a ganglioside complex consisting of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) are found in sera from patients with Guillain–Barré syndrome (GBS). To elucidate the clinical significance of anti-GM1/GalNAc-GD1a antibodies in GBS, clinical features of 58 GBS patients with IgG anti-GM1/GalNAc-GD1a antibodies confirmed by enzyme-linked immunosorbent assay and thin layer chromatography immunostaining were analyzed. Compared to GBS patients without anti-GM1/GalNAc-GD1a antibodies, anti-GM1/GalNAc-GD1a-positive patients more frequently had a preceding respiratory infection (n = 38, 66%, p < 0.01) and were characterized by infrequency of cranial nerve deficits (n = 9, 16%, p < 0.01) and sensory disturbances (n = 26, 45%, p < 0.01). Of the 28 anti-GM1/GalNAc-GD1a-positive patients for whom electrophysiological data were available, 14 had conduction blocks (CBs) at intermediate segments of motor nerves, which were not followed by evident remyelination. Eight of 10 bedridden cases were able to walk independently within one month after the nadir. These results show that the presence of anti-GM1/GalNAc-GD1a antibodies correlated with pure motor GBS characterized by antecedent respiratory infection, fewer cranial nerve deficits, and CBs at intermediate sites of motor nerves. The CB may be generated through alteration of the regulatory function of sodium channels in the nodal axolemma.     

Long term disability and social status change after Guillain–Barré syndrome

Objective Even if the majority of patients with Guillain–Barré syndrome (GBS) have a favourable functional outcome some residual motor and sensory signs and symptoms may remain. The aim of this study was to evaluate the long–term effect of GBS on daily life,working activities, hobbies and social status and the presence of residual symptoms. Patients and methods Seventy patients with GBS enrolled in a case–control study were examined. Information on signs or symptoms during the acute phase of the disease was retrieved from medical records and an ad–hoc questionnaire administered during hospitalization. Patients were interviewed by phone 3 to 5 years after disease onset about residual symptoms and changes in daily living. Disability and handicap were assessed using the Hughes, Rankin and Rotterdam 9–items scale. Results At follow–up 45 patients (64 %) made a complete functional recovery; 19 patients (27%) had some minor limitations in daily life although they were able to perform all their activities independently while 6 (9 %) needed aid for some hours or continuously during the day. Nineteen patients (27 %) had, however, to make substantial changes in their job, hobbies or social activities. There was no significant correlation between clinical and laboratory features during the acute phase of GBS and outcome. Conclusions Althoough over 90% of our GBS patients had a more or less complete functional recovery, almost 30% of them had to make substantial changes in daily life. These findings indicate that GBS still has a significant impact on patients' life which may go beyond their residual disability or impairment. Treatment of GBS should not be only aimed at improving patients' disability but also at limiting the impact of the disease on their social life.     

Long-term outcome in patients with Guillain–Barré syndrome requiring mechanical ventilation

We aimed to determine long-term disability and quality of life in patients with Guillain–Barré syndrome (GBS) who required mechanical ventilation (MV) in the acute phase. Our retrospective cohort study included 110 GBS patients admitted to an intensive care unit and requiring MV (01/1999–08/2010) in nine German tertiary academic medical centers. Outcome was determined 1 year or longer after hospital admission using the GBS disability scale, Barthel index (BI), EuroQuol-5D (EQ-5D) and Fatigue Severity Scale. Linear/multivariate regression analysis was used to analyze predicting factors for outcome. Mean time to follow up was 52.6 months. Hospital mortality was 5.5 % and long-term mortality 13.6 %. Overall 53.8 % had a favorable outcome (GBS disability score 0–1) and 73.7 % of survivors had no or mild disability (BI 90–100). In the five dimensions of the EQ-5D “mobility”, “self-care”, “usual activities”, “pain” and “anxiety/depression” no impairments were stated by 50.6, 58.4, 36.4, 36.4 and 50.6 % of patients, respectively. A severe fatigue syndrome was present in 30.4 % of patients. Outcome was statistically significantly correlated with age, type of therapy and number of immunoglobulin courses. In GBS-patients requiring MV in the acute phase in-hospital, and long-term mortality are lower than that in previous studies, while long-term quality of life is compromised in a large fraction of patients, foremost by immobility and chronic pain. Efforts towards improved treatment approaches should address autonomic dysfunction to further reduce hospital mortality while improved rehabilitation concepts might ameliorate long-term disability.     

Proximal nerve lesions in early Guillain–Barré syndrome: implications for pathogenesis and disease classification

Guillain–Barré syndrome (GBS) is an acute-onset, immune-mediated disorder of the peripheral nervous system. In early GBS, arbitrarily established up to 10 days of disease onset, patients could exhibit selective manifestations due to involvement of the proximal nerves, including nerve roots, spinal nerves and plexuses. Such manifestations are proximal weakness, inaugural nerve trunk pain, and atypical electrophysiological patterns, which may lead to delayed diagnosis. The aim of this paper was to analyze the nosology of early GBS reviewing electrophysiological, autopsy and imaging studies, both in acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor/motor-sensory axonal neuropathy (AMAN/AMSAN). Early electrophysiology showed either well-defined demyelinating or axonal patterns, or a non-diagnostic pattern with abnormal late responses; there may be attenuated M responses upon lumbar root stimulation as the only finding. Pathological changes predominated in proximal nerves, in some studies, most prominent at the sides where the spinal roots unite to form the spinal nerves; on very early GBS endoneurial inflammatory edema was the outstanding feature. In the far majority of cases, spinal magnetic resonance imaging showed contrast enhancement of cauda equina, selectively involving anterior roots in AMAN. Both in AIDP and AMAN/AMSAN, ultrasonography has demonstrated frequent enlargement of ventral rami of C5–C7 nerves with blurred boundaries, whereas sonograms of upper and lower extremity peripheral nerves exhibited variable and less frequent abnormalities. We provide new insights into the pathogenesis and classification of early GBS.     

A fatal case of Churg–Strauss syndrome presenting with acute polyneuropathy mimicking Guillain–Barré syndrome

A 64-year-old woman, with asthma and sinusal polyposis in her history, suddenly developed a painful polyneuropathy with diplopia. Nerve conduction studies, performed at the very onset of the neuropathy, could not definitely rule out a Guillain–Barré syndrome (GBS) and high-dose i.v. immunoglobulins were administered. Clinical and laboratory findings subsequently supported the diagnosis of Churg–Strauss syndrome; corticosteroid therapy was started and clinical stabilisation of neuropathy was apparently achieved. No indicators of unfavourable outcome were present at that time. Nevertheless, 30 days after the onset the patient acutely worsened with severe polyneuropathy relapse and fatal systemic diffusion to heart, kidney and mesenteric district, which a single cyclophosphamide pulse failed to control. This case highlights the possibility that a GBS-like onset of Churg–Strauss syndrome neuropathy should be regarded as a part of multiorgan, severe or even life-threatening vasculitic involvement, requiring the most aggressive treatments, regardless of the presence of recognised factors of poor outcome.     

Guillain–Barré syndrome as a parainfectious manifestation of SARS-CoV-2 infection: A case series

The global SARS-CoV-2 pandemic posed an unprecedented challenge to almost all fields of medicine and Neurology is not an exception. Collecting information about its complications and related conditions will help clinicians to become more confident in managing this disease. Guillain-Barre Syndrome (GBS) is mostly described as a post-infectious phenomenon and its occurrence during acute phase of illness is of interest. GBS has recently been reported during the active phase of COVID-19 for the first time. Severity and fast progression of GBS associated with COVID-19 have also been shown in recent studies. Here we report three cases of GBS during the active phase of COVID-19 with severe symptoms and fast progression to quadriplegia and facial diplegia over 2 days, which led to death in one case due to severe autonomic dysfunction. We suggest SARS-CoV-2 might be associated with rather a severe, rapidly progressive and life-threatening phenotype of GBS.     

Heart rate variability and baroreflex sensitivity abnormalities in Guillain–Barré syndrome: a pilot study

Clinical Autonomic Research - The current study aimed to investigate autonomic dysfunction in Guillain–Barré syndrome (GBS) patients and describe the results of computational heart rate...     

Campylobacter jejuni DNA-binding protein from starved cells in Guillain–Barré syndrome patients

Campylobacter jejuni enteritis is frequently associated with an axonal form of Guillain–Barré syndrome (GBS) and C. jejuni DNA-binding protein from starved cells (C-Dps) induces paranodal myelin detachment and axonal degeneration through binding with sulfatide in vivo. Here we investigated the invasion of C-Dps into hosts with C. jejuni-related GBS. Our analyses of patient sera found that both C-Dps and anti-C-Dps antibodies were most commonly detected in sera from C. jejuni-related GBS patients (5/27, 14.8% and 15/24, 62.5%; respectively). These findings suggest that C-Dps invades the host and may potentially contribute to the peripheral nerve damage in C. jejuni-related GBS.