Are early post-discharge physician contacts associated with 30-day psychiatric re-hospitalisation? A nationwide claims data based retrospective cohort study in Austria free of immortal time bias.

OBJECTIVES: Cost containment and quality of care considerations have increased research interest in the potential preventability of early re-hospitalisations. Various registry-based retrospective cohort studies on psychiatric re-hospitalisation have focused on the role of early post-discharge service contacts, but either did not consider their time-dependent nature ('immortal time bias') or evaded the issue by analysing late re-hospitalisations. The present study takes care of the immortal time bias in studying early psychiatric re-hospitalisations. METHODS: In a retrospective cohort study using nationwide electronic claims data in Austria, 10,689 adults discharged from acute psychiatric inpatient wards were followed up for 30 days. Cox regression analyses were performed with post-discharge psychiatric and general practitioner contacts as time-dependent covariates and time to first psychiatric re-hospitalisation as outcome. RESULTS: Post-discharge ambulatory physician contacts were significantly associated with a decreased psychiatric re-hospitalisation rate (hazard ratio 0.77 [95% CI 0.69; 0.87], p < 0.0001), with similarly strong contributions to this association by general practitioners and psychiatrists. CONCLUSIONS: Despite avoiding the immortal time bias and controlling for several confounders, we suggest to be cautious with a causal interpretation of the identified association, since potentially relevant confounders, such as disease severity, were unavailable in our claims data base.

Effects of paediatric intensive care due to congenital heart defects on maternal mental health.

AIM: Successful mother-child-bonding is a fundamental step for a healthy development of the child. Different factors like postpartum depression can hinder the bonding process. This study aimed to investigate how intensive care treatment due to congenital heart diseases of the infant alters bonding and how mothers cope with the situation. METHODS: Validated questionnaires were used to analyse postpartum depression, mother-child bonding, stress factors and coping strategies for mothers at a paediatric intensive care unit (PICU; n = 38) and a group of mothers without known psychiatric disorders attending a babywell visit with their child (n = 91). Descriptive statistics and interaction models were calculated. RESULTS: The PICU group showed on average higher total scores on the postpartum bonding questionnaire indicating mother-child bonding impairment and a higher proportion of mothers with depression was observed (76% vs 11%). The model showed a significant interaction between effective coping strategies and mother infant bonding (p = 0.04). Ineffective coping had no effect on bonding or depression in the PICU group. CONCLUSION: Mothers of children treated at an ICU due a congenital heart disease are at increased risk for the development of depression and difficulties in different aspects of postpartum bonding. Our results show that coping mechanisms might significantly influence postpartum bonding. Implementation of tailored support is needed to optimise maternal outcomes.

Safety of nurse-directed triage intranasal fentanyl protocol for acute pain management in a European pediatric emergency department: A retrospective observational analysis.

Background: Nurse-directed pain protocols for intranasal fentanyl administration are not widely implemented in European (EU) pediatric emergency departments (PED). Barriers include perceived safety concerns for intranasal (IN) fentanyl. The aim of this study is to describe our experience with a nurse-directed triage IN fentanyl protocol with a focus on safety in a tertiary EU PED. Methods: We conducted a retrospective analysis of patient records of children aged 0-16 years who received nurse-directed IN fentanyl between January 2019 and December 2021 at the PED of the University Children's Hospital of Bern, Switzerland. Extracted data points included demographics, presenting complaint, pain score, IN fentanyl dosage, concomitant pain medication use, and adverse events. Results: A total of 314 patients were identified with ages ranging from 9 months to 15 years. The main indication for nurse-directed fentanyl administration was musculoskeletal pain due to trauma (n = 284, 90%). Mild adverse events (vertigo) were reported in two patients (0.6%), without a correlation to concomitant pain medication or protocol violation. The only reported severe adverse event of syncope and hypoxia in a 14-year-old adolescent occurred in a setting where the institutional nurse-directed protocol was violated. Conclusion: In accordance with previous studies outside of Europe, our data support the case that when appropriately used, nurse-directed IN fentanyl is a safe potent opioid analgesic for pediatric acute pain management. We strongly encourage the introduction of nurse-directed triage fentanyl protocols Europe-wide in order to provide effective and adequate acute pain management in children.

Statins in nonsurgical and surgical periodontal therapy. A systematic review and meta-analysis of preclinical in vivo trials.

The cholesterol-lowering drugs, statins, possess anti-inflammatory, antimicrobial and pro-osteogenic properties, and thus have been tested as an adjunct to periodontal treatment. The present systematic review aimed to answer the following focused research question: What is the effect of local and/or systemic statin use on periodontal tissues in preclinical in vivo studies of experimentally induced periodontitis (EIP) and/or acute/chronified periodontal defect (ACP) models? A literature search (of Medline/PubMed, Embase/Ovid, CENTRAL/Ovid) using the following main eligibility criteria was performed: (i) English or German language; (ii) controlled preclinical in vivo trials; (iii) local and/or systemic statin use in EIP and/or ACP models; and (iv) quantitative evaluation of periodontal tissues (i.e., alveolar bone level/amount, attachment level, cementum formation, periodontal ligament formation). Sixteen studies in EIP models and 7 studies in ACP models evaluated simvastatin, atorvastatin or rosuvastatin. Thirteen of the EIP (81%) and 2 of the ACP (29%) studies presented significantly better results in terms of alveolar bone level/amount in favor of statins. Meta-analysis based on 14 EIP trials confirmed a significant benefit of local and systemic statin use (P < .001) in terms of alveolar bone level/amount; meta-regression revealed that statin type exhibited a significant effect (P = .014) in favor of atorvastatin. Three studies reported a significantly higher periodontal attachment level in favor of statin use (P < .001). Complete periodontal regeneration was never observed; furthermore, statins did not exert any apparent effect on cementum formation. Neither local nor systemic use of statins resulted in severe adverse effects. Statin use in periodontal indications has a positive effect on periodontal tissue parameters, supporting the positive results already observed in clinical trials. Nevertheless, not all statins available have been tested so far, and further research is needed to identify the maximum effective concentration/dose and optimal carrier.

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels-A pilot study.

BACKGROUND: Administration of the therapeutic anti-IgE antibody omalizumab to patients induces strong increases in IgE antibody levels. OBJECTIVE: To investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen-specific IgE in patients with birch pollen allergy. METHODS: Based on the fact that intranasal allergen application induces rises of systemic allergen-specific IgE, we performed a double-blind placebo-controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen-specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen-specific IgE levels and omalizumab-IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL-4/anti-CD40-treated PBMCs from allergic patients were studied in vitro. RESULTS: Intranasal challenge with Bet v 1 induced increases in Bet v 1-specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen-specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL-4/anti-CD40-induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE-omalizumab complexes were observed after subcutaneous administration of omalizumab. CONCLUSION: Intranasal administration of allergen induced rises of allergen-specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen-specific IgE levels.

EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis.

BACKGROUND AND PURPOSE: Tick-borne encephalitis (TBE) is an infection of the central nervous system (CNS) caused by tick-borne encephalitis virus (TBEV) and transmitted by ticks, with a variety of clinical manifestations. The incidence of TBE in Europe is increasing due to an extended season of the infection and the enlargement of endemic areas. Our objectives are to provide recommendations on the prevention, diagnosis and management of TBE, based on evidence or consensus decisions. METHODS: For systematic evaluation, the literature was searched from 1970 to 2015 (including early online publications of 2016), and recommendations were based on evidence or consensus decisions of the Task Force when evidence-based data were not available. RECOMMENDATIONS: Vaccination against TBE is recommended for all age groups above 1 year in highly endemic areas (≥5 cases/100 000/year), but also for individuals at risk in areas with a lower incidence. Travellers to endemic areas should be vaccinated if their visits will include extensive outdoor activities. Post-exposure prophylaxis after a tick bite is not recommended. A case of TBE is defined by the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis with cerebrospinal fluid (CSF) pleocytosis (>5 × 106 cells/l) and the presence of specific TBEV serum immunoglobulin M (IgM) and IgG antibodies, CSF IgM antibodies or TBEV IgG seroconversion. TBEV-specific polymerase chain reaction in blood is diagnostic in the first viremic phase but it is not sensitive in the second phase of TBE with clinical manifestations of CNS inflammation. Lumbar puncture should be performed in all patients with suspected CNS infection unless there are contraindications. Imaging of the brain and spinal cord has a low sensitivity and a low specificity, but it is useful for differential diagnosis. No effective antiviral or immunomodulating therapy is available for TBE; therefore the treatment is symptomatic. Patients with a potentially life threatening meningoencephalitis or meningoencephalomyelitis should be admitted to an intensive care unit. In the case of brain oedema, analgosedation should be deepened; osmotherapy and corticosteroids are not routinely recommended. If intracranial pressure is increased, therapeutic hypothermia or decompressive craniectomy might be considered. Seizures should be treated as any other symptomatic epileptic seizures. CONCLUSIONS: Tick-borne encephalitis is a viral CNS infection that may result in long-term neurological sequelae. Since its incidence in Europe is increasing due to broadening of endemic areas and prolongation of the tick activity season, the health burden of TBE is enlarging. There is no effective antiviral treatment for TBE, but the disease may be effectively prevented by vaccination.

Quality of life and comorbidities in palmoplantar pustulosis - a cross-sectional study on 102 patients.

BACKGROUND: Association of palmoplantar pustulosis (PPP) with metabolic and autoimmune diseases has been reported in mostly small case series or anecdotal cases. OBJECTIVE: To assess health-related quality of life and prevalence of comorbidities in a large cohort of PPP patients. METHODS: We conducted a cross-sectional study on patients with either active or past PPP. Disease severity was measured by the Palmoplantar Pustulosis Area and Severity Index (ppPASI). Quality of life was assessed by the Dermatology Life Quality Index (DLQI). Comorbidities were evaluated by medical history, blood examination, stool testing for Helicobacter pylori antigen and screening tools for depression and psoriatic arthritis. RESULTS: A total of 102 patients (87 women, 15 men) with a mean age of 52.6 ± 14.1 years were evaluated. The mean DLQI was 7 ± 6. Comorbidities were frequent and consisted of hypercholesterolaemia (38%), hypertension (32%), obesity (27%), metabolic syndrome (26%), depression (24%), diabetes (19%), autoimmune thyroiditis (16%) and psoriatic arthritis (16%). CONCLUSION: Patients with PPP have an impaired quality of life and a broad range of comorbidities. Contrary to other reports, our investigation failed to show an association between PPP and coeliac disease or H. pylori infection.

Assessment of efficacy and safety of the herbal medicinal product BNO 1016 in chronic rhinosinusitis.

BACKGROUND: The objective of this clinical trial (CRS-02) was to assess the efficacy, safety and tolerability of two dosages of the herbal medicinal product BNO 1016 (Sinupret extract) in patients with chronic rhinosinusitis (CRS). METHODOLOGY: 929 patients suffering from CRS were enrolled in this randomised placebo-controlled trial with a treatment period of 12 weeks. The primary endpoint was the mean Major Symptom Score (MSS) in week 8 and week 12 compared to placebo. Secondary endpoints included further MSS related parameters and responder rates over time. Pharmacoeconomic endpoints were also analysed. Finally, safety and tolerability were evaluated. RESULTS: Sinupret extract was not superior over placebo regarding the primary endpoint. However, the results of the secondary endpoints showed a clear trend towards superior efficacy. Therefore, additional post-hoc sensitivity analyses were performed in patients with a baseline MSS over 9 and persistence of disease more than 1 year diagnosed by specialists in otorhinolaryngology. Those patients significantly benefited from Sinupret extract. Therapy was superior for the primary endpoint analysis. Patients were less impaired with respect to work and daily activities. A good safety and tolerability of Sinupret extract was assured in all patients. CONCLUSIONS: Sinupret extract can safely be administered in patients with CRS. Although the primary endpoint of the study was not significant, a post-hoc subgroup analysis in patients whose disease was diagnosed by a specialist revealed a pronounced treatment effect. Effects in that subgroup were even stronger with longer disease persistence and stronger severity.

Identification of matrix metalloproteinase-12 as a candidate molecule for prevention and treatment of cardiometabolic disease.

Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predispose to the development of the cardiometabolic diseases: atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Prevention of metabolic syndrome requires novel interventions to address this health challenge. The objective of this study was the identification of candidate molecules for the prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie type 2 diabetes mellitus and cardiovascular disease, respectively. We used an unbiased bioinformatics approach to identify molecules that are upregulated in both conditions by combining murine and human data from a microarray experiment and meta-analyses. We obtained a pool of eight genes that were upregulated in all the databases analysed. This included well known and novel molecules involved in the pathophysiology of type 2 diabetes mellitus and cardiovascular disease. Notably, matrix metalloproteinase 12 (MMP12) was highly ranked in all analyses and was therefore chosen for further investigation. Analyses of visceral and subcutaneous white adipose tissue from obese compared to lean mice and humans convincingly confirmed the up-regulation of MMP12 in obesity at mRNA, protein and activity levels. In conclusion, using this unbiased approach an interesting pool of candidate molecules was identified, all of which have potential as targets in the treatment and prevention of cardiometabolic diseases.

Diagnostic criteria of chronic inflammatory demyelinating polyneuropathy in diabetes mellitus.

OBJECTIVE: The possibility of co-association between diabetes mellitus (DM) and chronic inflammatory demyelinating polyneuropathy (CIDP) has long been a focus of interest as well as of clinical significance. As CIDP is a potentially treatable condition, it is diagnosis in the context of DM is of great importance. However, diagnostic criteria to identify CIDP in patients with diabetes are not available. We propose a diagnostic tool that should help clinicians to decide what is the probability that a patient with diabetes might have CIDP. METHODS: We list several clinical, electrophysiological, and laboratory parameters that, when combined, have the power of discriminating an immune-mediated neuropathy in patients with DM. By summing the points assigned to each of these parameters, we define four levels of probability for a patient with diabetes to have CIDP. To analyze the validity of the diagnostic toll, we applied it in three different patient populations: (i) Patients with diabetes with peripheral neuropathy, (ii) Patients with CIDP without DM, and (iii) Patients with diabetes with CIDP. RESULTS: The scores of patients with diabetes without CIDP ranged from -7 to 2, while those of patients with DM-CIDP ranged from 2 to 20. The scores of non-diabetic patients with CIDP were similar to those of patients with DM-CIDP and ranged from 6 to 16. The mean score of patients with DM-CIDP was 9.083, while the score of patients with CIDP was 11.16 and that of patients with diabetic polyneuropathy was -3.59. CONCLUSIONS: These results show that this diagnostic tool is able to identify patients with diabetes with overlapping CIDP.

Tumefactive demyelination and a malignant course in an MS patient during and following fingolimod therapy.

Finglimod, a sphingosine 1-phosphate receptor modulator, is the first orally administered therapy approved for prophylaxis in multiple sclerosis (MS). Several reports in the last two years suggested that it might be associated with severe augmentation of disease activity upon initiation or discontinuation of therapy. We present an MS patient who developed a giant cavitating brain lesion under fingolimod and in whom cessation of therapy was associated with a very active course. Brain biopsy revealed the lesion to be due to an active demyelinating inflammatory process. With the current wave of immunosuppressive treatments for MS, there is a need to be vigilant to side effects and risks not identified in large multicenter trials, collect the data and set guidelines and precautions for present and future medications.

Maintenance IVIg therapy in myasthenia gravis does not affect disease activity.

OBJECTIVES: There is insufficient data on the efficacy of intravenous immunoglobulins (IVIg) as maintenance treatment in myasthenia gravis (MG). We therefore examined response to maintenance IVIg therapy in a cohort of MG patients. METHODS: We reviewed all MG patient files treated with IVIg in our neuro-immunology clinic from 1/1995 to 9/2012. Patients treated with maintenance IVIg for a minimum of one year were separately analyzed. Disease severity was evaluated according to the Myasthenia Gravis Foundation of America clinical classification. RESULTS: IVIg was considered for maintenance therapy in 52 MG patients who had not responded to pyridostigmine, prednisone, azathioprine or combinations of these drugs. Fifteen patients did not improve with initial IVIg while thirty seven patients had a beneficial response and were treated with maintenance IVIg for an average of 5.9 years (range 1-17 years). Twenty two (59%) patients were female with an average age onset of disease 44.8 years. Thirty three were seropositive for acetylcholine receptor antibody and 13 had previous thymectomy. Twenty three and 14 patients achieved mild or moderate improvement respectively in disease activity while on IVIg therapy but none achieved full remission. Beneficial response was associated with older age, bulbar presentation, seropositivity and a higher antibody titer and less with ocular presentation. IVIg enabled reduction of other treatments including pyridostigmine, prednisone and azathioprine. CONCLUSION: In this retrospective study on a relative small cohort of MG patients maintenance IVIg therapy was successful in reducing symptoms of MG but seems to be ineffective in inducing full remission or reducing disease activity. IVIg should be regarded only as symptomatic therapy in MG.

The role of aquaporin-1 in idiopathic and drug-induced intracranial hypertension.

Idiopathic intracranial hypertension is a common disorder affecting mainly healthy, young, overweight women. The pathogenesis of this condition is unknown, but it has been shown to follow treatment with several compounds including corticosteroids and vitamin A derivatives. This paper will offer a novel hypothesis and insight on the pathogenesis of drug induced intracranial hypertension following a review and analysis of the literature. Both corticosteroids and vitamin A derivatives have been shown to upregulate the expression of aquaporin 1, a water channel protein. Aquaporin 1 is widely distributed in the human brain and is associated with water secretion into the subarachnoid space. Aquaporin 1 was also shown to participate in the regulation of weight. Agents used for treating idiopathic intracranial hypertension reduce aquaporin 1 expression. Based on these observations, we propose that aquaporin 1 has a pathogenetic role in drug induced idiopathic intracranial hypertension. Over expression of this gene causes increased intracranial pressure, and downregulation reduces pressure and alleviates the symptomatology and complications of idiopathic intracranial hypertension.

Genotyping of Bacillus anthracis isolated from Croatia and Bosnia and Herzegovina.

Anthrax is a serious disease caused by Bacillus anthracis. Humans can become infected by handling products from infected animals, by breathing spores and rarely by eating undercooked meat from infected animals. The genome of B. anthracis is highly monomorphic and thus shows very low DNA sequence variation. We analysed the molecular characteristics of 12 B. anthracis isolates from outbreaks in Croatia and Bosnia and Herzegovina, which have occurred during the past 10 years along with two vaccine strains. Genotyping system based on variable-number tandem repeat analysis at six loci revealed that six isolates belong to genotype from the A1.a cluster whilst six isolates relate to the B2 cluster, compared to 89 previously described genotypes. The distribution of two evolutionarily distant clusters suggests an introduction of B. anthracis to this area in at least two separate events.

EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections of the nervous system.

BACKGROUND: Polymerase chain reaction (PCR) as a means to amplify nucleic acids has become an essential element in diagnosis of infections. It has evolved into a simple and rapid, easy- to- use approach. At present there are no published guidelines for the usage of PCR technology for the diagnosis of infections of the nervous system. METHODS: We reviewed the advantages and pitfalls of PCR in order to guide neurologists and infectious diseases experts in its application for the diagnosis of infections of the nervous system. Medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in May 2012. Recommendations were reached by consensus. RECOMMENDATIONS: The reliability of PCR technology for the diagnosis of neurological infections is currently based on the pathogens. The main contribution of PCR is to the diagnosis of viral infections followed by bacterial CNS infections with the notable exception of tuberculous meningitis. Efficacy for the diagnosis of protozoal infections and helminthic infestations has also been established in many instances. Unfortunately, current molecular PCR technology is far from becoming routine in resource-poor countries where such infections are prevalent. Despite the importance of fungal infections in the context of the immune-compromised host, there is not enough data to recommend the routine use of PCR. CONCLUSIONS: PCR technology is currently a reliable method for the diagnosis of viral and bacterial (except tuberculosis) infections, and only for some protozoal infections and helminthic infestations.

Dose response of tramadol and its combination with paracetamol in UVB induced hyperalgesia.

Combining tramadol with paracetamol is an established analgesic treatment strategy. However, dosing and differential effects on peripheral and central hyperalgesia are still to be determined. After Ethics Committee approval, 32 volunteers have been included in this 2 phased, double blinded, placebo controlled, cross-over study. A defined small skin area was irradiated with a UVB source inducing hyperalgesia. Twenty-four hours after irradiation, heat pain-, cold pain threshold (HPPT, CPPT), mechanical pain sensitivity to pin prick (MPS) in the area of pin prick hyperalgesia (AsH) and MPS in the sunburn were determined. In phase I, measurements have been repeated 30 min after receiving cumulative 0.3, 0.6 and 1 mg/kg of intravenous (i.v.) tramadol or active placebo. Only at 1 mg/kg tramadol and solely for MPS in the sunburn a reduction to placebo could be demonstrated (p = 0.024). Accordingly in phase II, the trial has been repeated using 1 mg/kg tramadol and paracetamol or placebo in a cumulative i.v. dose of 330, 660 and 990 mg. Now the addition of 330 mg paracetamol to tramadol reduced thermal hyperalgesia by 1.15 °C (CI 0.55; 1.76). This effect, however, did not increase with higher doses. Tramadol showed week anti-hyperalgesia reducing CPPT, MPS and AsH compared to baseline measurements (p < 0.05). Paracetamol also reduced secondary hyperalgesia, but no combination effect with tramadol could be shown. We conclude, in inflammatory hyperalgesia tramadol alone exerts only weak anti-hyperalgesia. Even adding a small dose paracetamol enhances thermal anti-hyperalgesia.

Basophils are not the key antigen-presenting cells in allergic patients.

BACKGROUND: Recent data obtained in mouse models have initiated a controversy whether basophils are the key antigen-presenting cells (APCs) in allergy. Here, we investigate whether basophils are of importance for the presentation of allergen and the induction of T cell proliferation in allergic patients. METHODS: T cells, basophils, and APCs depleted of basophils were purified from allergic patients. Co-culture systems based on purified major allergens were established to study allergen-specific T cell responses using proliferation assays. RESULTS: Only co-cultures of T cells with APCs depleted of basophils but not with basophils proliferated in response to allergen. Even addition of IL-3 to T cell-basophil co-cultures failed to induce allergen-specific T cell proliferation. CONCLUSIONS: Our data demonstrate by classical in vitro proliferation assays that basophils are not key antigen-presenting cells that promote T cell proliferation in secondary immune responses to allergen in allergic patients.

Sudden sensorineural hearing loss in multiple sclerosis: clinical course and possible pathogenesis.

OBJECTIVE - To assess the symptom of sudden hearing loss in multiple sclerosis (MS). METHOD - We reviewed patient files in our MS clinic between January 2004 and November 2009 for symptoms of sudden hearing loss. RESULTS - We were able to identify 11 of 253 patients (4.35%) with sudden hearing loss. In seven patients, the hearing decline was the presenting symptom of MS and in all 11 patients, it appeared early in the course of the disease. There was no residual hearing deficit in 9/11 patients. In no patient was the condition bilateral and in none did it recur. CONCLUSION - Episodes of hearing loss are not uncommon in MS and have a good chance of complete recovery.

Transient immunosuppression: a bridge between infection and the atypical autoimmunity of Guillain-Barré syndrome?

Guillain-Barré syndrome (GBS) is an acute, usually monophasic, disorder of the peripheral nervous system that is assumed to be of immune-mediated pathogenesis. However, several clinical features and experimental findings of GBS are uncharacteristic for an immune-mediated disorder and set this condition apart from other disorders with a putative immune-mediated pathogenesis. These features include, among others, the monophasic nature of GBS, the lack of response to immunosuppressive (unlike immunomodulatory) therapy, the absence of a typical association with immunogenetic background and the inability to establish a valid and relevant animal model. We suggest a comprehensive hypothesis for the pathogenesis of GBS that is based on the assumption that the condition is due to a transient (or occasionally chronic) immune deficiency, as in most cases GBS follows an infection with pathogens known to induce immunosuppression. Such infections may be followed by breakdown of immune tolerance and induction of an immune attack on peripheral nerves. Mounting of the immune-mediated assault might be triggered either by the same infective pathogen or by secondary infection. Clearance of the infection and resumption of a normal immune response and tolerance eventually terminate the immune-mediated damage to the peripheral nerves and enable recovery. This hypothesis assumes that the entire sequence of events that culminates in GBS is due to transient exogenous factors and excludes a significant role for inherent host susceptibility, which explains the monophasic nature of the disorder.