Improving the sensitivity of myelin oligodendrocyte glycoprotein-antibody testing: exclusive or predominant MOG-IgG3 seropositivity-a potential diagnostic pitfall in patients with MOG-EM/MOGAD.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated. OBJECTIVE: To assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing. METHODS: Re-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion). RESULTS: In accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 [93%] samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 [55%] patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 [32%] patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA+/IgG- MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested. CONCLUSIONS: In some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and-just like H+L- and Fcγ-specific testing-might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted.

Newly emerging type B insulin resistance (TBIR) during treatment with eculizumab for AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD): fatal outcome.

BACKGROUND: Aquaporin-4 immunoglobulin G (AQP4-IgG) antibody-positive neuromyelitis optica spectrum disorders (NMOSD) are frequently associated with other autoimmune disorders, including systemic lupus erythematosus (SLE). Eculizumab (ECU) is a highly effective long-term treatment for NMOSD. However, ECU is known to increase significantly the risk of infection with encapsulated bacteria and sepsis. Recently, increased insulin resistance (IR) in patients with NMOSD has been suggested. Type B IR (TBIR) is a rare autoimmune condition often accompanying or preceding SLE. TBIR has not yet been reported in NMOSD. OBJECTIVE: To report an ECU-treated patient with AQP4-IgG-positive NMOSD who developed fatal septic complications after the emergence of TBIR. METHODS: Description of the clinical course over a period of 8 years. RESULTS: A female patient was diagnosed with NMOSD at the age of 16 years. A variety of disease-modifying drugs failed to achieve sufficient disease control, resulting in severe tetraparesis. Treatment with ECU was started 6 years after NMOSD diagnosis and stabilized the disease. The patient developed TBIR 8 months after initiation of ECU therapy. Following high-dose intravenous methylprednisolone therapy for a clinical relapse and three further courses of ECU, the patient was admitted with severe pneumonia caused by the encapsulated bacterium Klebsiella pneumoniae and hypoglycemia. Despite multimodal therapy, the patient died from sepsis-related multiorgan failure 18 months after initiation of ECU. CONCLUSIONS: TBIR should be considered as differential diagnosis in patients with NMOSD presenting with disturbed glucose metabolism, irrespective of the presence of SLE. More real-world data are needed on the risk/benefit ratio of ECU treatment in patients who have co-existing autoimmune comorbidities that may compromise immune function. Strategies to mitigate the risk of serious infection in patients treated with ECU are discussed.

[Diffusion-weighted MRI - how many B-values are necessary?]. / Diffusionsgewichtete MRT - wie viele Diffusionsfaktoren sind notwendig?

PURPOSE: Diffusion-weighted imaging (DWI) has become an important component in modern stroke imaging. This MR technique detects diffusion abnormalities, which can be quantified by computing apparent diffusion coefficient (ADC) maps. ADC values are typically calculated from a set of MR images obtained with varying degrees of diffusion weighting (b-values) using nonlinear regression. However, there is no agreement concerning the number of images needed for ADC calculation. The aim of our study was to determine how many b-values are necessary to reliably calculate ADC maps. MATERIALS AND METHODS: In 100 consecutive patients with clinical signs of acute ischemic stroke, 6 identically oriented and centered diffusion data sets with different b-values were acquired. ROI analysis was performed for DWI-positive lesions, normal-appearing gray and white matter, CSF, and background noise. ADC values for each ROI were calculated using a nonlinear regression model. Additionally, the CNR and SNR were calculated for each ROI. RESULTS: Acquisition time was 0:39 min for 2 b-values and up to 2:49 min for a sequence with 7 b-values. The mean ADC (× 10(-3) mm2/s) for ischemic lesions was 58.29, 58.47, 57.83, 57.81, 57.58 and 54.51 using 2, 3, 4, 5, 6, and 7 b-values. Ischemic lesions had significantly different mean ADC values only for high b-values (b = 2000 s/mm2). CONCLUSION: ADC values can be reliably calculated using 2 b-values. Radiologists may use the more time-efficient 2-point method for reliably estimating ADC values and detecting ischemic lesions in the daily clinical routine.

Micro flow modules with combined fluid flow channel and optical detection waveguide--hyper Rayleigh scattering as a case study.

Micro flow modules with optical detection have been fabricated in a way which enables optical waveguiding inside and a defined interaction length along the fluid channel. Because of the usually lower refractive index of the solution compared with that of the substrate, so-called "leaky" optical wave-guiding must be employed. The combination of the fluid flow channel function with that of the optical waveguide has advantages for all miniaturized optical detection cells. It has been shown for hyper Rayleigh scattering (HRS) that improvement of the analytical principle is inherent in the miniaturization. The detection limit can be enhanced by at least a factor of 20. The applied HRS measurement procedure also enables simultaneous detection of two photon absorption (TPA) fluorescence. The severe boundary conditions of capillary electrophoresis were used as micro flow module design constraints to enable the transfer of the approach to other types of analysis.

Laparoscopic repair of cholecystoduodenal fistula: report of two cases.

BACKGROUND: Laparoscopic surgery has become the standard of care for benign gallbladder disease. PATIENTS AND METHODS: We treated two middle-aged women having acute exacerbations of chronic gallbladder disease with laparoscopic cholecystectomy. A cholecystoduodenal fistula was diagnosed intraoperatively in each case. These fistulae were repaired laparoscopically using an endoscopic stapling device without complication. RESULTS: Each patient did well postoperatively and was discharged to home on the second postoperative day in good condition. CONCLUSIONS: Biliary-enteric fistula is a known complication of chronic gallbladder disease that is traditionally considered a contraindication to laparoscopic cholecystectomy. However, we believe laparoscopic repair to be a safe and effective approach in the hands of surgeons with significant laparoscopic experience.

Herniation of the gastric wall through a Nissen fundoplication.

Two patients presented several years after Nissen fundoplication with dysphagia and/or hemorrhage. In both, the fundoplication was intact in the original relationship to the cardia but herniated gastric wall was found between the fundic wrap and the distal end of the esophagus. The diagnosis and alternatives for preventing this problem are presented.

Acute transanal ileal evisceration.

This is the 31st report of spontaneous transanal evisceration of small bowel. This case is unique because a rectal prolapse had been repaired previously and at the time of evisceration, there was no evidence of recurrence. Inherent or acquired weakness of the anterior rectal wall combined with a sudden increase in intra-abdominal pressure appears to precipitate this rare phenomenon. Attention to basic surgical tenets applies in the management of this condition.