Acute painful autoimmune neuropathy: A variant of Guillain-Barré syndrome.

INTRODUCTION: We present a painful small-fiber neuropathy variant of Guillain-Barré syndrome characterized by antecedent infectious symptoms, hyporeflexia, and albuminocytologic dissociation. METHODS: Two patients received intravenous immunoglobulin, one corticosteroids. RESULTS: The patients subsequently improved. Immunoglobulin G (IgG) antibodies in their acute phase sera strongly bound to murine small nerve fibers, and the binding disappeared during the convalescent phase. Serum transfer to a murine nociceptive model induced transient alteration in thermal pain responses. DISCUSSION: Our case series suggest that an acute transient immune response can be directed against small nerve fibers, and that patients so affected can exhibit features of Guillain-Barré syndrome. Muscle Nerve 57: 320-324, 2018.

Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: We report the clinical and serologic features of Japanese patients with chronic inflammatory demyelinating polyneuropathy (CIDP) displaying anti-neurofascin-155 (NF155) immunoglobulin G4 (IgG4) antibodies. METHODS: In sera from 533 patients with CIDP, anti-NF155 IgG4 antibodies were detected by ELISA. Binding of IgG antibodies to central and peripheral nerves was tested. RESULTS: Anti-NF155 IgG4 antibodies were identified in 38 patients (7%) with CIDP, but not in disease controls or normal participants. These patients were younger at onset as compared to 100 anti-NF155-negative patients with CIDP. Twenty-eight patients (74%) presented with sensory ataxia, 16 (42%) showed tremor, 5 (13%) presented with cerebellar ataxia associated with nystagmus, 3 (8%) had demyelinating lesions in the CNS, and 20 of 25 (80%) had poor response to IV immunoglobulin. The clinical features of the antibody-positive patients were statistically more frequent as compared to negative patients with CIDP (n = 100). Anti-NF155 IgG antibodies targeted similarly central and peripheral paranodes. CONCLUSION: Anti-NF155 IgG4 antibodies were associated with a subgroup of patients with CIDP showing a younger age at onset, ataxia, tremor, CNS demyelination, and a poor response to IV immunoglobulin. The autoantibodies may serve as a biomarker to improve patients' diagnosis and guide treatments.

Sialylated IgG-Fc: a novel biomarker of chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: Sialylation in Fc portion of IgG plays a crucial role in the pathogenesis of autoimmune diseases and the working mechanism of intravenous immunoglobulin (IVIG). We aim to test whether IgG-Fc sialylation is a biomarker of disease activity for chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: By using specific lectins for sialylation, galactosylation and agalactosylation, lectin-enzyme assay and lectin blotting with pretreatment of IgG degradating enzyme of Streptococcus pyogenes were performed to compare the glycosylation levels of serum IgG-Fc (1) between patients of untreated CIDP (n=107) and normal control subjects (n=27), (2) among patients with untreated CIDP of different clinical severities and (3) before and after IVIG treatment of patients with CIDP (n=12). RESULTS: Sialylation and galactosylation of IgG-Fc were significantly reduced in patients with CIDP than normal control subjects (p=0.003 and 0.033, respectively), whereas agalactosylation was increased in CIDP (p=0.21). Ratios of sialylated/agalactosylated IgG-Fc levels were significantly reduced in CIDP (p<0.001) and inversely related to disease severity (p=0.044). After IVIG treatment, levels of sialylated IgG-Fc significantly increased (p=0.003). CONCLUSIONS: Sialylation of IgG-Fc is reduced in CIDP. Its level correlated with clinical severity and increased after IVIG treatment. Sialylated as well as ratio of sialylated/agalactosylated IgG-Fc could be new measures to monitor the disease severity and treatment status in CIDP.

Autoimmune inflammatory neuropathies: updates in pathogenesis, diagnosis, and treatment.

PURPOSE OF REVIEW: The present review aims at discussing the recent advances in pathogenesis, diagnosis, and treatment of major subtypes of autoimmune inflammatory neuropathies. RECENT FINDINGS: Concerning pathogenesis, further evidence has proved that antibodies to nodal proteins are pathogenic in inflammatory neuropathies. The presence of these antibodies is related to distinctive clinical features. Disruption of blood-nerve barrier mediated by cytokines and chemokines also plays an important role in the pathogenesis. The new terminology of 'nodopathies' describes immune-mediated attack beginning and limited to the nodal region, and this phenomenon can be found in both acute and chronic inflammatory neuropathies. Recent trials comparing intravenous and subcutaneous immunoglobulin confirm that subcutaneous immunoglobulin is not only cost-effective, but also improves patients' satisfaction and quality of life compared to intravenous immunoglobulin. Although immunotherapies are effective in most of the inflammatory neuropathies, accurate predictors and biomarkers of treatment response are lacking. Moreover, some patients do not respond to current immunotherapies and continue to relapse after discontinuation of treatment. SUMMARY: More studies are required to understand the exact antigenic targets and mechanism in inflammatory neuropathies, so as to develop more novel immunotherapies.

Telephone and Teleradiology-Guided Thrombolysis Can Achieve Similar Outcome as Thrombolysis by Neurologist On-site.

BACKGROUND: Because of the limitation of on-site neurology workforce, telestroke was implemented to overcome this barrier. We explored the efficacy and safety of intravenous (IV) stroke thrombolysis service by telestroke when neurologist was not available on-site. METHODS: From January 2009 to December 2012, we compared patients treated with IV stroke thrombolysis by telestroke in the form of telephone consultation with teleradiology, to patients treated after in-person assessment by the same team of neurologists in a regional hospital. Door-to-needle time, symptomatic intracranial hemorrhage, and functional outcome at 3 months were prospectively collected and compared between the groups. RESULTS: In all, 152 patients were treated with IV thrombolysis; 102 patients were treated with neurologist on-site; whereas 50 patients were treated by internists with telestroke. Fifty-two percent of the telemedical group achieved excellent outcome compared to 43% of the neurologist on-site group (P = .30). Symptomatic intracranial hemorrhage rate (4.0% versus 4.9%, P = 1.0) and mortality (8.3% versus 11.9%, P = .49) were comparable. Using the multiple logistic regression analysis, age, baseline stroke severity, and extent of early ischemic change on brain computed tomography scan, are independent predictors for excellent outcome, whereas the presence of neurologist on-site is not correlated with the outcome. CONCLUSIONS: Patients treated without neurologist on-site achieved similar outcome. Telephone consultation and teleradiology-guided IV stroke thrombolysis, with the support of on-site internist appeared safe and efficacious.

Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia.

A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option.

Cytoalbuminologic dissociation in Asian patients with Guillain-Barré and Miller Fisher syndromes.

Cerebrospinal fluid (CSF) protein level, cell count, and its relationship to the timing of lumbar puncture were collected from patients with Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) from various Asian centers. A total of 507 patients with GBS were studied. Overall, 56% had elevated CSF protein level. This was significantly lower than that reported in a recent Dutch study (56% vs 64%). Cytoalbuminologic dissociation was also lower in the Asian cohort (55% vs 64%), with a significantly higher proportion of patients with mild pleocytosis (26% vs 15%). A lower proportion of the 164 patients with MFS had elevated CSF protein level (38% vs 56%), mild pleocytosis (11% vs 26%), and cytoalbuminologic dissociation (41% vs 55%) compared to patients with GBS. In both conditions, cytoalbuminologic dissociation was linked to the timing of lumbar puncture. Cytoalbuminologic dissociation was only observed in half of the Asian patients with GBS and MFS, and it is strongly dependent on the timing of the lumbar puncture.