Left ventricular function in myasthenia gravis.

Myasthenia gravis is an autoimmune disorder with autoantibodies to acetylcholine receptors of skeletal muscle. Left ventricular diastolic function was studied with M-mode and Doppler echocardiography in 25 patients with myasthenia and in a group of age- and heart rate-matched control subjects. In the patients, diastolic peak filling rate was reduced by 37%, and Doppler peak early filling velocity (E) was reduced by 12% compared with the control subjects (2.7 +/- 0.7 vs 4.2 +/- 1.0 s-1, and 76 +/- 8 vs 85 +/- 15 cm/s, respectively; p less than 0.05). Peak atrial filling velocity (A) was increased by 38% (68 +/- 17 vs 48 +/- 9 cm/s; p less than 0.01), and consequently the E:A ratio in the group of patients was reduced by 33% (1.22 +/- 0.40 vs 1.81 +/- 0.33; p less than 0.001). End-diastolic dimension was 5.0 +/- 0.5 cm in both groups, heart rate was 70 +/- 12 vs 68 +/- 16 beats/min (p = not significant [NS]), M-mode ejection fraction was 76 +/- 8 vs 79 +/- 5% (p = NS), M-mode peak ejection rate was -1.9 +/- 0.4 vs -2.1 +/- 0.3 s-1 (p = NS), and peak aortic outflow velocity was 109 +/- 18 vs 98 +/- 13 cm/s (p = NS). Twenty-three patients and 15 control subjects were studied before and after intake of the acetylcholine-esterase inhibitor pyridostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ryanodine receptor autoantibodies in myasthenia gravis patients with a thymoma.

Sera from patients with myasthenia gravis were examined by Western blot for the presence of antibodies to proteins of the sarcoplasmic reticulum from rabbit skeletal muscle. Fourteen of 30 patients with myasthenia gravis and a thymoma had IgG autoantibodies to the calcium release channel of the sarcoplasmic reticulum (the ryanodine receptor), which plays a crucial role in the mechanism of excitation-contraction coupling in striated muscle. Ryanodine receptor autoantibodies were not detected in any of the 45 sera from patients with myasthenia gravis without a thymoma. Ryanodine receptor autoantibodies may have pathogenetic relevance in thymoma-associated myasthenia gravis.     

Ryanodine receptor antibodies in myasthenia gravis: epitope mapping and effect on calcium release in vitro

Patients with myasthenia gravis can have antibodies against skeletal muscle ryanodine receptor (Ry1), the sarcoplasmic reticulum calcium-release channel, which plays a crucial role in excitation-contraction coupling. We have screened a panel of overlapping Ry1 fusion proteins with Ry1 antibody-containing myasthenia gravis sera to identify the main immunogenic region. The pc2 Ry1 fusion protein representing a Ry1 region close to the N-terminus (residues 799-1172) was identified as the main immunogenic region for the antibodies. The binding kinetics of the Ry1 antibodies to the pc2 Ry1 fusion protein were tested using an optical biosensor. Ry1 antibodies in the IgG fraction from sera of patients with myasthenia gravis bound with high affinity and with a stoichiometry of 1:1. The functional effect of these Ry1 antibodies was tested in an in vitro Ca2+-release assay. The Ry1 antibodies induced a twofold increase of the half-maximal concentration for 4-Cl-m-cresol-induced Ca2+ release from terminal cisternae vesicles but had no effect on V(max). The effect on 4-Cl-m-cresol-induced Ca2+ release was specific, as preincubation of the active IgG fraction with the pc2 Ry1 fusion protein abolished the inhibition. These data suggest that the Ry1 sequence defined by residues 799-1172 is involved in the regulation of Ry1 function, and that this regulation could be functionally affected in vivo in patients with myasthenia gravis.     

Sensitivity and specificity of a commercial C6 peptide enzyme immuno assay in diagnosis of acute Lyme neuroborreliosis

The purpose of this study was to evaluate the diagnostic sensitivity and specificity of a commercial C6 enzyme immuno assay, QuickC6, in acute Lyme neuroborreliosis (LNB) in endemic areas. Paired sera and cerebral spinal fluids (CSFs) from 60 patients with definite LNB, eight patients with possible LNB, 18 patients with conditions mimicking LNB and 42 persons with noninfectious neurological disease were examined. The case definition of LNB was based on strict criteria during a prospective 4-month follow-up. The sensitivity of QuickC6 was 98% both in sera and CSFs, and the diagnostic specificity was 61% in sera and 88% in CSFs. QuickC6 is a sensitive, simple and cost-effective screening test in serum and CSF in diagnosis of acute LNB. Specificity needs further evaluation.     

Chronic daily headache with medication overuse: predictors of outcome 1 year after withdrawal therapy

Background and purpose:  We examined prospectively the results of withdrawal therapy in 80 patients with probable medication overuse headache. The aim was to identify baseline patient characteristics that might predict outcome after 1 year (end of study).
Methods:  We classified patients according to results of withdrawal therapy measured as the improvement of headache days (HD) from baseline to end of study.
Results:  Thirty-six per cent (29/80) had at least 50% improvement. Sixty-four per cent (51/80) had <50% improvement, and among these, 30% (24/80) had <10% improvement. The following baseline characteristics were associated with poor outcome of withdrawal therapy: use of codeine-containing drugs, low self-reported sleep quality, and high self-reported bodily pain as measured by the quality of life tool SF-36.
Conclusion:  Before suggesting withdrawal therapy, one should probably pay more close attention to sleep problems.     

Chronic polyneuropathy and Lyme disease

Infection of the peripheral nervous system with Borrelia burgdorferi can present as a cranial neuropathy or radiculopathy with cerebrospinal fluid (CSF) pleocytosis and intrathecal antibody production against B. burgdorferi , or as an asymmetric peripheral neuropathy with acrodermatitis chronica atrophicans (ACA) and normal CSF findings. According to North American studies, it can also present as a symmetric chronic polyneuropathy without ACA or other Lyme manifestations. Our purpose was to investigate the prevalence of B. burgdorferi antibodies in patients presenting with isolated chronic polyneuropathy (PN) in a European region with high incidence of Lyme disease. Sera from 209 PN patients and 247 healthy blood donors from Vest-Agder County, Norway, were examined. Borrelia burgdorferi antibodies were detected in 43 (21%) PN patients and in 45 (18%) healthy blood donors ( P  = 0.553). The prevalence of B. burgdorferi antibodies was similar ( P  = 0.311) in cryptogenic PN (24/102, 24%) and PNs of identified etiologies (19/107, 18%). PN patients with B. burgdorferi antibodies had normal spinal fluid white cell count and they did not differ clinically or electrophysiologically from PN patients without antibodies. None of 20 antibody-positive PN patients responded to antimicrobial treatment. The study shows that, in Europe, chronic distal PN without ACA or other Lyme manifestations is very rarely caused by a B. burgdorferi infection.     

Lyme neuroborreliosis: do we treat according to guidelines?

Journal of Neurology - Evidence-based guidelines, published in 2010, equate the efficacy of oral and intravenous antibiotics and recommend treatment duration of 2&nbsp;weeks in early Lyme...     

Myasthenia gravis patients with a thymoma have antibodies against a high molecular weight protein in sarcoplasmic reticulum.

Our purpose was to investigate whether components of the sarcoplasmic reticulum (SR) are relevant antigens in myasthenia gravis (MG). Using enzyme-linked immunosorbent assay (ELISA), 75 MG sera and 120 control sera were examined for IgG antibodies against SR prepared from rabbit skeletal muscle. 16/30 thymoma MG patients had IgG antibodies that reacted with SR. 1/30 MG patients with thymic hyperplasia and 3/15 MG patients with thymic atrophy had SR antibodies in low concentrations. Control sera were negative. Using immunoblot, SR antibodies were detected in the thymoma group only. 14/30 sera from thymoma patients reacted with a protein of 320 kDa relative molecular weight. The only reported SR protein with similar electrophoretic mobility is the subunit of the spanning protein which links junctional SR to sarcolemma and functions as a calcium-release channel.