Acute Phase Of Guillain-Barré Syndrome Research Articles

Sympathetic skin response (SSR) in pediatric Guillain-Barré syndrome.

In the present study, sympathetic skin response (SSR) characteristics were explored in children with Guillain-Barré syndrome (GBS) and the value of early diagnosis and prognostic evaluation in GBS complicated by autonomic dysfunction (AD) was evaluated. A total of 25 children with GBS and 30 healthy controls (HCs) were enrolled in this prospective study. SSR findings for the two groups were compared. SSR and nerve conduction study (NCS) results were compared among patients with GBS, and differences in clinical characteristics between the groups with abnormal and normal SSR were analyzed. Within the GBS group, six patients (24%) required mechanical ventilation, 17 patients (66.7%) had AD, 18 patients (72%) had an abnormal SSR, and 13 patients (52%) had AD combined with SSR abnormalities. There was a statistically significant difference in SSR latency in the lower limbs between the GBS group and HCs (P < 0.05). There was no statistically significant difference between SSR and NCS results in the acute phase of GBS (P > 0.05), and there was no significant difference in the rate of AD or in Hughes functional grade at nadir between the groups with abnormal and normal SSR (P>0.05). However, there was a statistically significant difference between the results of SSR and NCS tests during the recovery phase (P = 0.003). Abnormal SSR mainly occurred in cases of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype. In addition, SSR was abnormal in all pediatric GBS patients with poor prognosis 1 month after onset of symptoms. Two-thirds of the children with GBS have AD. SSR could be used for early diagnosis and follow-up of GBS and may also be helpful in evaluating disease severity and short-term prognosis.

Validation of elevated levels of interleukin-8 in the cerebrospinal fluid, and discovery of new biomarkers in patients with GBS and CIDP using a proximity extension assay.

Biomarkers for diagnosis of inflammatory neuropathies, assessment of prognosis, and treatment response are lacking. CSF and EDTA plasma from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), healthy controls (HC) and disease controls were analyzed with Olink multiplex proximity extension assay (PEA) from two independent cohorts. Levels of interleukin-8 (IL8) were further analyzed with ELISA in patients with GBS, CIDP, paraproteinemia-related demyelinating polyneuropathy (PDN), multifocal motor neuropathy (MMN), HC and disease controls. ROC analysis was performed. Outcome was measured with the GBS-disability score (GBS-ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) score. In CSF, multiplex PEA analysis revealed up-regulation of IL8 in GBS compared to CIDP and HC respectively, and CIDP compared to HC. In addition, levels of IL2RA were upregulated in GBS compared to both HC and CIDP, SELE in GBS compared to HC, and ITGAM, IL6, and NRP1 in GBS compared to CIDP. In plasma, levels of MMP3, THBD and ITGAM were upregulated in CIDP compared to HC. Validation of multiplex IL8 results using ELISA, revealed increased levels of IL8 in CSF in patients with GBS and CIDP versus HC and non-inflammatory polyneuropathies (NIP) respectively, as well as in PDN versus NIP and HC. Levels of IL8 in CSF correlated with impairment in the acute phase of GBS as well as outcome at 6-months follow up. IL8 in CSF is validated as a diagnostic biomarker in GBS and CIDP, and a prognostic biomarker in GBS. Multiplex PEA hereby identifies several potential biomarkers in GBS and CIDP.

Responsiveness of 2 Different Ability Outcome Measures in Guillain-Barré Syndrome.

The most frequently used ability outcome measure in Guillain-Barré syndrome (GBS) is the GBS disability scale (GDS). Recently developed inflammatory Rasch-built overall disability (I-RODS) scale has been suggested to be used in inflammatory polyneuropathies. In the present study, we wanted to assess the comparative responsiveness of I-RODS and GDS in subjects who were diagnosed with GBS during a follow-up period of 6 months. Our prospective, multicentric study included 72 subjects. Patients were tested, using GDS and I-RODS, on day 14, day 28, month 3, and month 6 from the start of the symptoms. We defined improvement as a reduction for 1 or more points on GDS or improvement on I-RODS as defined by Draak (2014). Between days 14 and 28 there was an improvement in 28% of patients as measured with GDS and only in 10% patients as measured with I-RODS. At month 3 compared with day 14, we noticed an improvement in GDS score in 90% of GBS patients and I-RODS score in 65%. At month 6 improvements were noticed in 94% of patients measured by GDS and 78% according to I-RODS. Our findings support the use of GDS in an acute phase of GBS. I-RODS have their role mostly during a longer follow-up period when the majority of patients are ambulant and their other abilities besides walking are also of great importance.

P-PN024. The profile of cerebrospinal fluid analysis in patients with Guillain-Barré Syndrome

Introduction . Guillain-Barré Syndrome (GBS) is a clinical syndrome of an acute inflammatory polyradiculoneuropathy with ascending muscle weakness. One of the criteria to diagnose GBS is including the cerebrospinal fluid examination. Several parameters had been analysed from this examination. During the acute phase of GBS, characteristic findings on CSF analysis include albuminocytologic dissociation, which is an elevation of CSF protein (>0.55 g/L) without an elevation of white blood cells. In this study, we describe the profile of cerebrospinal fluid analysis in patients with GBS. Methods . Thirty-three adult patients with GBS were retrospectively analysed from medical record in Dr.Sardjito General Hospital, Yogyakarta, collected from January 2016 to September 2019. Results . The age of patients ranged from 18 to 77 years. The proportion of male was higher than female (21 vs 12 patients). The cerebrospinal fluid analysis found that the mean white blood cells count was 17,82 ± 44,965 cells/µL, range from 0 to 200 (normal result 0–5 cells/µL). The mean protein count was 0,13242 ± 0,147098 g/dL, ranged from 0,010 to 0,800 (normal result 0,02–0,05 g/dL). The albuminocytologic dissociation result was found in 21 of 33 patients (63,64%). The mean of glucose level was 91,4848 ± 22,439 mg/dL, ranged from 68 to 188 (normal result 50–80 mg/dL). Conclusion . Cerebrospinal fluid analysis showed the elevation of white blood cells count, protein count and glucose level in GBS patients. More than half of the results showed albuminocytologic dissociation.

Psychiatric Sequelae of Guillain-Barré Syndrome: Towards a Multidisciplinary Team Approach.

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune polyneuropathy. Recent research has highlighted that GBS is associated with the onset of psychiatric symptoms which represent a burden for patients and close relatives. However, acute psychiatric sequelae due to GBS may be misinterpreted as ‘intensive care unit (ICU) delirium’. This review outlines the existing evidence for the psychiatric symptoms associated with GBS with a view to improving psychoeducation of patients. The main psychiatric symptoms of GBS that have been reported in the literature include, stress, anxiety, depression, fatigue, sleep abnormalities, visual hallucinations, paranoid delusions, disorientation, terror and psychosis. These psychiatric symptoms, which occur during the acute phase of GBS, if not recognised and treated, may progress to long-term psychiatric problems that interfere with improvement of physical symptoms. A multidisciplinary team approach to the management of GBS may improve both physical and psychiatric recovery.

Autoimmunity and cytokines in Guillain-Barré syndrome revisited: review of pathomechanisms with an eye on therapeutic options.

Guillain-Barré syndrome (GBS) is the most common cause of acute paralysis in the United States. Campylobacter jejuni is a common trigger for GBS, igniting autoimmunity as a result of molecular mimicry between C.jejuni lipooligosaccharide (LOS) and host gangliosides. Evidence also suggests an active role for cell-mediated and innate immunity in pathogenesis of GBS. Infection alone is not enough for GBS to develop, infection with the same strain might yield different outcomes in different patients. C.jejuni strains with low to absent molecular mimicry to self-antigens can cause full-blown GBS with positive autoantibodies. A role for T helper 17 and IL-17 in acute phase of GBS is also identified. Currently, no biological treatment is validated for severe, ventilation-dependent patients with GBS, who might not benefit from either IVIG or plasma exchange therapy. Use of biologic agents in treatment-resistant GBS, especially anti-IL-17 agents, such as secukinumab, ixekizumab, and brodalumab, is to be hoped. This review covers up-to-date knowledge on autoimmune mechanisms responsible in different subtypes of GBS: acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy; as well as the experimental autoimmune neuritis (EAN), a commonly used animal model of GBS.

Pain during the acute phase of Guillain-Barré syndrome.

In this study, we tried to describe the characteristics of pain and explore the association between the incidence of pain and abnormal laboratory test results in patients during the acute phase of Guillain–Barré syndrome (GBS).This retrospective cohort study enrolled 252 patients with GBS who were in the acute phase of the disease. We collected data regarding the location and type of pain, the onset time, clinical variables and laboratory tests, including the levels of uric acid (UA), albumin, cerebrospinal fluid protein (CSFP), cerebrospinal fluid glucose (CSFG), fasting glucose upon admission, and blood creatinine. The pain descriptors were compared to the severity of disease and laboratory examination results.Around 34.5% of the patients reported pain during the acute phase of GBS. Pain was negatively correlated with the disease severity during the acute phase. In total, 29 of the 87 (33.3%) patients reported pain during the 2 weeks preceding the onset of weakness. The concentration of CSFP was positively associated with the incidence of pain, while the concentrations of UA and albumin were not correlated with the incidence of pain.We found that 33.3% of the GBS patients experienced pain within 2 weeks of onset, and the pain was positively associated with CSFP concentration but was not correlated with disease severity.

IL-23 and IL-27 Levels in Serum are Associated with the Process and the Recovery of Guillain-Barr\xe9 Syndrome

IL-23 and IL-27 are believed to be involved in the pathogenesis of Guillain-Barré syndrome (GBS). However, changes in these cytokines during the dynamic pathological and recovery processes of GBS are not well described. In the present study, plasma was collected from 83 patients with various stages of GBS, 70 patients with central nervous system demyelinating diseases,70 patients with other neurological diseases (OND) and 70 age- and sex-matched healthy volunteers. Serum levels of IL-23, IL-27, and Campylobacter jejuni (CJ) IgM were assessed using enzyme linked immunosorbent assay (ELISA). We found that serum IL-23 levels of patients during the acute phase of GBS were significantly higher followed by a decreasing trend during the recovery phase of the disease. Serum IL-27 levels significantly increased during the acute phase of GBS, and gradually increased during the recovery phase. Interestingly, both the severity and subtype of GBS were closely associated with the two cytokines. IL-23 levels were positively correlated with IL-27 levels, prognosis, and other clinical parameters. Our findings confirm that IL-23 may show pro-inflammatory effects, especially at the early stage of GBS. IL-27 appears to have a dual role in GBS, with initial pro-inflammatory effects, followed by anti-inflammatory properties during recovery.

P1. Follow-Up ultrasonography of the peripheral nervous systems in Guillain–Barré syndrome (GBS)

Ultrasonography of the peripheral nervous system (PNUS) and its ability to visualize nerve alteration including cervical nerve roots and the vagal nerve in acute phase of Guillain–Barre syndrome (GBS) has been reported. The objective of this study was to evaluate long-term results of PNUS and nerve conduction studies (NCS) over a time period of at least six month. PNUS and/or NCS of several peripheral nerves, the vagal nerve and the cervical nerve roots 5 and 6 were performed in 24 patients with GBS at day 1–3 after symptom onset, one week after five-day immunoglobulin therapy (IVIG) and after six month. Data were compared to 30 healthy controls. In the acute phase of GBS, significant differences – not surprisingly – were found concerning NCS. Moreover, significant nerve enlargement was found in almost all nerves, but not in the sural nerve compared to healthy controls. The vagal nerve was also significantly enlarged, most prominent in patients with autonomic symptoms (p Figure ) as well as the C5 and C6 root diameter, which showed a significant correlation to the amount of CSF-protein (Pearson correlation, p

Association of ubiquitin carboxy-terminal hydrolase-L1 in cerebrospinal fluid with clinical severity in a cohort of patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyneuropathy. Although its pathogenic mechanism has been revealed and various therapeutic trials have been performed, a proportion of patients experience the severe sequelae associated with GBS. In this paper, we investigated whether the amount of the neuron-specific protein, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), in the cerebrospinal fluid of patients with GBS was correlated with the clinical course of the disease. UCH-L1 protein levels were greater in patients with GBS than in controls. The patients with GBS whose UCH-L1 protein levels were higher than those of the controls presented with more severe symptoms at peak. UCH-L1 protein levels tended to become elevated as the total protein levels were increased; however, elevated UCH-L1 without an increase in total protein might be correlated with severe disease course (bedridden or ventilator supported). These results suggest that UCH-L1 could be a biomarker associated with the severity of the disease at the acute phase of GBS.

Ultrasonography of the peripheral nervous system in the early stage of Guillain-Barré syndrome.

Ultrasonography can be used to visualize peripheral nerve abnormalities in immune-mediated neuropathies. The objective of this study was to prove the role of ultrasonography (US) in acute phase of Guillain-Barré syndrome (GBS). Systematic ultrasonic measurements of several peripheral nerves including the vagal nerve as well as the sixth cervical nerve root were performed in 18 patients with GBS at days 1-3 after symptom onset and compared to 21 healthy controls. Nerve conduction studies (NCS) of corresponding nerves were undertaken. Consequently, significant differences between the groups were found in compound muscle action potential amplitudes, F-wave latency, and persistency. Ultrasonic cross-sectional areas (CSAs) showed significant enlargement in all nerves except of the ulnar nerve (upper arm) and the sural nerve compared to healthy controls, most prominent in proximal and middle median nerve (p < 0.01). The vagal nerve also showed enlargement compared to controls (p < 0.05), which was most pronounced in patients with autonomic dysfunction compared to patients without (p < 0.05). C6 root diameter showed a significant correlation to the amount of cerebrospinal fluid (CSF)-protein (Pearson correlation, p < 0.05). US shows nerve enlargement in several peripheral nerves including vagal nerve and C6 root in acute phase of GBS and could be an additional diagnostic tool for example, in GBS of atypical onset and autonomic dysfunction.

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.

Prevalence of anti-ganglioside antibodies and their clinical correlates with guillain-barré syndrome in Korea: a nationwide multicenter study.

Background and PurposeNo previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barré syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance.MethodsSerum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody.ResultsAmong 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) by a single electrophysiological study.ConclusionsAnti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.

Elevated Levels of Cerebrospinal Fluid and Plasma Interleukin-37 in Patients with Guillain-Barré Syndrome

Aims. Interleukin-37 (IL-37) is an anti-inflammatory cytokine. This study aims to investigate the concentrations of plasma and cerebrospinal fluid (CSF) IL-37 in patients with Guillain-Barré Syndrome (GBS). Methods. The levels of plasma and CSF IL-37, IL-17A, IFN-γ, and TNF-α in 25 GBS patients and 20 healthy controls (HC) were determined by enzyme-linked immunoabsorbent assay and flow cytometric bead array assay, respectively. The values of clinical parameters in the patients were also measured. Results. The concentrations of plasma IL-37, IL-17A, IFN-γ, and TNF-α and CSF IL-37 and IL-17A in patients at the acute phase of GBS were significantly higher than those in the HC. The levels of plasma IL-37, IL-17A, IFN-γ, and TNF-α were positively correlated in those patients, and the levels of CSF IL-37 and IL-17A as well as the levels of plasma TNF-α were correlated positively with the GBS disability scale scores (GDSs) in those patients. Treatment with intravenous immunoglobulin significantly reduced the levels of plasma IL-37, IL-17A, IFN-γ, and TNF-α in the drug-responding patients. Conclusions. Our findings indicate higher levels of plasma and CSF IL-37 and IL-17A and other proinflammatory cytokines in patients with GBS.

CSF protein biomarkers for proximal axonal damage improve prognostic accuracy in the acute phase of Guillain‐Barré syndrome

Early predictors of prognosis in Guillain-Barré syndrome (GBS) are needed to identify patients who are likely to make a poor recovery and to guide therapeutic decision-making in the acute phase. Here we investigate whether axonal protein biomarkers released into the cerebrospinal fluid (CSF) following proximal axonal damage improve the early prognostic accuracy in GBS. A prospective multicenter study including 132 patients (38 GBS, 38 neurological controls, 42 headaches, 14 chronic inflammatory demyelinating neuropathy). CSF levels of axonal [neurofilament (NfH) and tau] and glial (S100B and glial fibrillary acidic protein) protein biomarkers were measured on admission. Nerve conduction studies were performed at the time of lumbar puncture and patients were classified according to neurophysiological criteria. Outcome was assessed on the Hughes functional score (F-score). Poor outcome was defined as the inability to walk independently (F-score > or = 3). High NfH levels (>0.73 ng/ml) predicted poor outcome (P = 0.01) with an odds ratio of 7.3 and correlated with the outcome F-score (R = 0.51, P < 0.01), as did hTau levels (R = 0.47, P < 0.01). Patients with poor outcome had significantly higher CSF NfH (median 1.78 ng/ml) when compared to those with good outcome (0.03 ng/ml) or all of the control groups (neurological controls 0.18 ng/ml, headaches 0.06 ng/ml, chronic inflammatory demyelinating neuropathy 0.05 ng/ml). Except for age (P < 0.05) and need for ventilatory support (P < 0.05), none of the other features reliably predicted outcome. Improved prognostic accuracy in the acute phase of GBS seems possible using CSF NfH levels.

Neuropsychological/-psychiatric deficits in immune-mediated neuropathies

Albeit common, neuropsychological/psychiatric deficits in patients with autoimmune-mediated neuropathies have not received much attention; however, they can impose a considerable clinical problem. Especially in intensive-care treated Guillain Barré syndrome (GBS) severe psychosis may occur which may go unrecognised due to the severity of the neurological motor deficits. Fatigue may result in a major restriction of quality of life long after the acute phase of GBS and is also a major debilitating factor in chronic inflammatory neuropathies. Symptomatic treatment remains largely empirical.

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

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. 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. 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. Although 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.

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 16

Antibodies to different neural antigens have been reported in patients with dysimmune neuropathies but their pathogenetic role in these diseases is still debated. In order to identify other possible protein target antigens in these diseases we tested by immunoblot IgG and IgM reactivity with human cauda equina and spinal cord in the sera from 30 patients with Guillain‐Barré syndrome (GBS), 14 with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and 11 with multifocal motor neuropathy (MMN). As controls we examined sera from 11 patients with amyotrophic lateral sclerosis (ALS), 68 with other neurological and non‐neurological diseases (OND) and 28 normal subjects. We found high titers (&gt;1/800) of IgG antibodies to some protein bands of the approximate molecular weight (MW) of 45–50 kDa in spinal cord but not cauda equina, in 20 patients (67%) with GBS, and 1 each with MMN and CIDP (9% and 7%, respectively)(GBS vs. MMN/CIDP p &lt; 0.05). In 16 GBS positive patients this reactivity was re‐tested and found reduced during recovery. A similar IgG reactivity with the 45–50 kDa bands was found in 2 patients (18%) with ALS (GBS vs. ALS p &lt; 0.05), 15 (23%) with OND (GBS vs. OND p &lt; 0.001) and in no normal subject. Since the MW of reactive bands corresponded to that of Glial Fibrillar Acidic Protein (GFAP), we tested the serum from 6 intensely positive GBS patients (titers of 1/6400 up to 1/12800) for IgG reactivity with purified GFAP by immunoblot. In four of them IgG bound to GFAP in a pattern similar to that observed with a commercial anti‐GFAP antibody. Pre‐incubation of one of these sera with purified GFAP completely abolished IgG reactivity with GFAP by immunoblot. This study shows that anti‐GFAP IgG antibodies are significantly increased during the acute phase of GBS and decrease during recovery. Further investigation is necessary to clarify their possible pathogenetic role in the disease.

IgG from patients with Guillain-Barré syndrome interact with nicotinic acetylcholine receptor channels.

In Guillain-Barré syndrome (GBS), immunoglobulin G (IgG) antibodies block neuromuscular transmission pre- and postsynaptically and thus are of potential pathogenic relevance. We investigated whether IgG from GBS patients has a direct interaction with nicotinic acetylcholine receptor (nAChR) channels. Purified IgG fractions from six GBS patients that blocked neuromuscular transmission in a previous study were analyzed by the patch-clamp technique in combination with an ultrafast system for solution exchange. Sera from three patients with other inflammatory neurological disorders were used as controls. Mouse myotubes expressing native embryonic-type nAChR channels and human embryonic kidney (HEK) 293 cells transiently transfected with recombinant adult-type nAChR channels were used. Repeated 20-ms pulses of acetylcholine (ACh) were applied to outside-out patches in the presence of GBS-IgG. IgG of the patients had a significant reversible blocking action on embryonic- and adult-type nAChR channels with some variability in the magnitude of the block. Activation and desensitization kinetics were not affected when GBS-IgG was applied. None of the control sera blocked the AChR channels. The observed postsynaptic block effect fulfills the criteria of a channel-blocking IgG antibody similar to those seen in autoimmune myasthenia and may contribute to muscle weakness during the acute phase of GBS.

IL-10 and IFN-γ in Guillain–Barré syndrome

Guillain–Barré syndrome (GBS) is an acute inflammatory disease affecting myelin and axons of the peripheral nervous system (PNS). GBS is considered to be caused by breakdown of tolerance to autoantigens of the PNS. The involvement of cytokines in GBS and in relation to treatment with high dose intravenous immunoglobulin (IvIg) is incompletely known. We studied the temporal profiles of IL-10 and IFN-γ-secreting blood mononuclear cells (MNC) over the course of GBS, using enzyme-linked immunospot (ELISPOT) assays. Pretreatment levels of blood MNC spontaneously secreting IL-10 were higher in the acute phase of GBS than in control patients with aseptic meningitis, other neurological diseases, diabetic neuropathy and healthy subjects. Levels of IFN-γ-secreting blood MNC were not increased over the course of GBS. Patients treated with IvIg had lower numbers of IL-10-secreting MNC compared to untreated patients. High levels of IL-10-secreting MNC correlated with serum anti-ganglioside IgM antibody levels, and with neurophysiological signs of axonal damage. The present data suggests that IFN-γ is not involved in GBS pathogenesis, and IL-10 being up-regulated in the early phase of GBS and associated with axonal damage, may have a pathogenetic role in GBS.