High and Persistent Anti-GM1 Antibody Titers Are Associated With Poor Clinical Recovery in Guillain-Barré Syndrome.

BACKGROUND AND OBJECTIVES: Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy that may follow a preceding infection inducing a cross-reactive antibody response to glycosphingolipids in peripheral nerves. The immune response in GBS is considered to be short lasting, explaining its monophasic clinical course. However, the disease course varies between patients, and residual deficits frequently occur. The duration of the antibody response has not been defined extensively in GBS, and the persistence of these antibodies may impair clinical recovery. The aim of this study was to determine the titer course of serum antibody titers to the ganglioside GM1 in relation to clinical course and outcome in patients with GBS. METHODS: Acute-phase sera from patients with GBS included in previous therapeutic trials were screened for anti-GM1 IgG and IgM antibodies in ELISA. Anti-GM1 antibody titers were determined in sera collected at entry and during a 6-month follow-up. Clinical course and outcomes were compared between groups based on the titer course. RESULTS: Anti-GM1 antibodies were detected in 78 (20.7%) of 377 included patients. The anti-GM1 IgG and IgM antibody titer course was highly variable between patients. A subset of anti-GM1-positive patients had persistent anti-GM1 antibodies at 3 months (n = 27/43 [62.8%]) and 6 months (n = 19/41 [46.3%]). Patients with a high anti-GM1 IgG and IgM titer at entry recovered more slowly and less complete than anti-GM1-negative patients (IgG: p = 0.015, IgM: p = 0.03). High vs low IgG titers were independently associated with poor outcome after correcting for known prognostic factors (p = 0.046). Among patients with a high anti-GM1 IgG titer at entry, a slow titer decline was associated with poor outcome at 4 weeks (p = 0.003) and 6 months (p = 0.032). Persistent high IgG titers at 3 and 6 months were associated with poor outcome at 6 months (3 months: p = 0.022, 6 months: p = 0.004). DISCUSSION: High anti-GM1 IgG and IgM antibody titers at entry and persistent high anti-GM1 IgG antibody titers are associated with poor outcome in patients with GBS. Antibody persistency indicates ongoing antibody production long after the acute disease state in GBS. Further research is required to determine whether antibody persistency interferes with nerve recovery and is a target for treatments.

[Influenza-associated acute necrotizing encephalitis: unknown makes undertreated?] / Influenza-geassocieerde acute necrotiserende encefalitis.

BACKGROUND: Influenza-associated acute necrotizing encephalitis (ANE) is a very rare, but severe complication from influenza infection. CASE DESCRIPTION: We present a 48 year old male who presented with fever, malaise, confusion and altered mental status (E4M5V2) and influenza A infection. He quickly develops convulsions after which he is intubated and admitted to the Intensive Care Unit following which he remains comatose (E1M1V1). The diagnosis of influenza associated acute necrotizing encephalitis is made based on his neurological symptoms, generalized slowing on electro-encephalogram, classic bilateral findings on MRI in the thalamus and basal ganglia and proven influenza infection in the cerebrospinal fluid. CONCLUSION: Acute necrotising encephalitis is a severe complication from a common infection. It is advised to consider early MRI imaging in patients with influenza and fitting neurological symptoms and to consider treatment with corticosteroids.

Guillain-Barré syndrome: pathogenesis, diagnosis, treatment and prognosis.

Guillain-Barré syndrome (GBS) is a potentially life-threatening postinfectious disease characterized by rapidly progressive, symmetrical weakness of the extremities. About 25% of patients develop respiratory insufficiency and many show signs of autonomic dysfunction. Diagnosis can usually be made on clinical grounds, but lumbar puncture and electrophysiological studies can help to substantiate the diagnosis and to differentiate demyelinating from axonal subtypes of GBS. Molecular mimicry of pathogen-borne antigens, leading to generation of crossreactive antibodies that also target gangliosides, is part of the pathogenesis of GBS; the subtype and severity of the syndrome are partly determined by the nature of the antecedent infection and specificity of such antibodies. Intravenous immunoglobulin and plasma exchange are proven effective treatments but many patients have considerable residual deficits. Discrimination of patients with treatment-related fluctuations from those with acute-onset chronic inflammatory demyelinating polyneuropathy is important, as these conditions may require different treatments. Novel prognostic models can accurately predict outcome and the need for artificial ventilation, which could aid the selection of patients with a poor prognosis for more-individualized care. This Review summarizes the clinical features of and diagnostic criteria for GBS, and discusses its pathogenesis, treatment and prognosis.

Paraparetic Guillain-Barré syndrome.

OBJECTIVE: To define the clinical and diagnostic characteristics of paraparetic Guillain-Barré syndrome (GBS) with weakness restricted to the legs, compared with the classic quadriparetic GBS. METHODS: Prospectively collected data from a cohort of 490 patients with GBS, previously involved in therapeutic or clinical studies, were used to define the demography, clinical presentation, diagnostic investigations, and clinical course in patients with paraparesis during a 6-month follow-up. RESULTS: Forty patients (8%) presented with a paraparesis without weakness of arms and hands. In 29 patients (73%), normal strength of upper extremities persisted during the follow-up period. Patients with paraparesis compared to patients with quadriparesis had a milder form of GBS, with less frequent cranial nerve involvement and less severe leg weakness, despite the fact that the majority of these patients were unable to walk unaided. Median time between onset of weakness and study entry was 6 days (interquartile range 4-11 days) for patients with paraparesis compared with 5 days (interquartile range 3-8 days) for patients with quadriparesis (p = 0.031). Fifty percent of patients with paraparesis presented with arm sensory deficits and 73% had reduced or absent arm reflexes. Nerve conduction studies demonstrated arm nerve involvement in 89% of these patients. At 6 months of follow-up, 98% of patients with paraparesis were able to walk unaided compared with 81% of the patients with quadriparesis (p = 0.008). There was no association between paraparesis and age, sex, or preceding infections. CONCLUSIONS: Paraparesis is an atypical clinical presentation or subform of GBS in which the diagnosis is usually supported by the presence of sensory deficits, reduced reflexes, or abnormal nerve conduction of the arms.

Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria.

Guillain-Barré syndrome is an acute polyradiculoneuropathy with a variable clinical presentation. Accurate diagnostic criteria are essential for patient care and research, including clinical trials and vaccine safety studies. Several diagnostic criteria for Guillain-Barré syndrome have been proposed, including the recent set by the Brighton Collaboration. In the present study we describe in detail the key diagnostic features required to meet these Brighton criteria in a study population of 494 adult patients with Guillain-Barré syndrome, previously included in therapeutic and observational studies. The patients had a median age of 53 years (interquartile range 36-66 years) and males slightly predominated (56%). All patients developed bilateral limb weakness which generally involved both upper and lower extremities. The weakness remained restricted to the legs in 6% and to the arms in 1% of the patients. Decreased reflexes in paretic arms or legs were found initially in 91% of patients and in all patients during follow-up. Ten (2%) patients however showed persistence of normal reflexes in paretic arms. Disease nadir was reached within 2 weeks in 80%, within 4 weeks in 97% and within 6 weeks in all patients. A monophasic disease course occurred in 95% of patients, of whom 10% had a treatment-related fluctuation. A clinical deterioration after 8 weeks of onset of weakness occurred in 23 (5%) patients. Cerebrospinal fluid was examined in 474 (96%) patients. A mild pleocytosis (5 to 50 cells/µl) was found in 15%, and none had more than 50 cells/µl. An increased cerebrospinal fluid protein concentration was found only in 64% of patients, highly dependent on the timing of the lumbar puncture after onset of weakness (49% at the first day to 88% after 2 weeks). Nerve electrophysiology was compatible with the presence of a neuropathy in 99% of patients, but only 59% fulfilled the current criteria for a distinct subtype of Guillain-Barré syndrome. Patients with a complete data set (335) were classified according to the Brighton criteria, ranging from a high to a low level of diagnostic certainty, as level 1 in 61%, level 2 in 33%, level 3 in none, and level 4 in 6% of patients. Patients categorized in these levels did not differ with respect to proportion of patients with preceding events, initial clinical manifestations or outcome. The observed variability in the key diagnostic features of Guillain-Barré syndrome in the current cohort study, can be used to improve the sensitivity of the diagnostic criteria.