Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined. Methods In this multi-institutional observational study (2007-2012), all patients with GluN1 antibodies were assessed at symptom onset and 4, 8, 12, 18, and 24 months using the modified Rankin Scale (mRS). Treatment included first-line immunotherapy (steroids, intravenous immunoglobulin, plasmapheresis), second-line immunotherapy (rituximab, cyclophosphamide), and tumor removal. Predictors of outcome were determined at the Universities of Pennsylvania and Barcelona using generalized linear mixed models with binary distribution. Results 577 patients (1-85 years, median 21) were studied, 212 were children (<18 years). Treatment effects and outcome were assessable in 501 (median follow-up 24 months): 472 (94%) underwent first-line immunotherapy or tumor removal, resulting in improvement within four weeks in 251 (53%). Of 221 patients who failed first-line therapy, 125 (57%) received second-line immunotherapy resulting in better outcome than those who did not (OR 2·69, CI 1·24-5·80, p=0·012). During the first 24 months, 394/501 reached good outcome (mRS 0-2; median 6 months), and 30 died. At 24 month follow-up 204/252 (81%) had good outcome. Outcomes continued to improve for up to 18 months after symptom onset. Predictors of good outcome were early treatment (OR 0·62, CI 0·50-0·76, p<0·0001) and lack of ICU admission (OR 0.12, CI 0·06-0·22,p<0·0001). 45 patients had one or multiple relapses (representing a 12% risk within 2 years); 46/69 (67%) relapses were milder than previous episodes (p<0·0001). In 177 children, predictors of good outcome and the magnitude of effect of second-line immunotherapy were comparable to those of the entire cohort. Conclusions Patients with anti-NMDAR encephalitis respond to immunotherapy. Second-line immunotherapy is usually effective when first-line therapies fail. Recovery can take more than 18 months.

Summary Background We aimed to assess the sensitivity/specificity of serum and CSF antibody-testing in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, and the correlation between titers, relapses, outcome, and epitope repertoire. Methods In this observational study, brain immunohistochemistry and cell-based assays (CBA) with fixed and live NMDAR-expressing cells were used to determine the sensitivity/specificity of antibody-testing in paired serum/CSF obtained at diagnosis of 250 patients with anti-NMDAR encephalitis and 100 control subjects. A patient was considered antibody-positive if either serum or CSF tested positive with both immunohistochemistry and CBA; titers were determined with serial sample dilution using brain immunohistochemistry. Samples from 45 patients (25 good-outcome: modified Rankin Scale [mRS] 0–2; 10 poor-outcome: mRS 3–6; 10 relapses) were examined at ≥3 disease time points. Epitope repertoire was determined with CBA expressing GluN1-NMDAR mutants Findings All 250 patients had NMDAR-antibodies in CSF but only 214/250 had antibodies in serum (sensitivity 100% [98.5–100%] versus 85.6% [80.7–89.4%], p<0.0001). Serum immunohistochemistry-testing was more often in agreement with CBA with fixed than live cells (77/108 versus 63/108, p=0.0056). In multivariable analysis, CSF and serum titers were higher in patients with poor-outcome than in those with good-outcome (CSF dilution 340 versus 129, difference 211, [95%-CI 1.1–421], p=0.049; serum 7370 versus 1243, difference 6127 [2369–9885], p=0.0025), and in patients with teratoma than in those without (CSF 395 versus 110, difference 285 [134–437], p=0.0079; serum 5515 versus 1644, difference 3870 [548–7193], p=0.024). Over time there was a decrease of antibody-titers regardless of outcome (from diagnosis to last follow-up: CSF 614 to 76, difference 538 [288–788]; serum 5460 to 1564, difference 3896 [2428–5362], both p<0.0001). Relapses correlated better with the titer-change in CSF than that in serum (14/19 versus 7/16, p=0.037). After recovery, 24/28 CSF and 17/23 serum from patients remained antibody-positive. Patients’ antibodies targeted a main epitope region at GluN1 aa369; the epitope repertoire did not differ between patients with different outcomes, and did not change during relapses. Interpretation NMDAR antibody-testing is more sensitive in CSF than serum. Antibody-titers in CSF and serum are higher in patients with poor-outcome or teratoma. The titer-change in CSF correlates better with relapses than that of serum. Funding The Dutch Cancer Society, the National Institute of Health, the McKnight Neuroscience of Brain Disorders award, the Fondo de Investigaciones Sanitarias, Erasmus MC fellowship and Fundació la Marató de TV3.

Objective: To describe the clinical features and outcome of anti-NMDA receptor (NMDAR) encephalitis in patients $45 years old.Method: Observational cohort study.Results: In a cohort of 661 patients with anti-NMDAR encephalitis, we identified 31 patients $45 years old. Compared with younger adults (18-44 years), older patients were more often male (45% vs 12%, p , 0.0001), had lower frequency of tumors (23% vs 51%, p 5 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p 5 0.009) and treatment (7 vs 4 weeks, p 5 0.039), and had less favorable outcome (modified Rankin Scale score 0-2 at 2 years, 60% vs 80%, p , 0.026). In multivariable analysis, younger age (odds ratio [OR] Conclusions: Anti-NMDAR encephalitis is less severe in patients $45 years old than in young adults, but the outcome is poorer in older patients. In this age group, delays in diagnosis and treatment are more frequent than in younger patients. The frequency of underlying tumors is low, but if present they are usually carcinomas instead of teratomas in younger patients. Early and aggressive immunotherapy will likely improve the clinical outcome. Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disorder that usually affects children and young adults, resulting in severe neuropsychiatric symptoms that often respond to treatment. [1][2][3][4] Experience with older patients is limited to a single case report 5 and series comprising patients of all ages, but no further information is available. We report a detailed clinical analysis of 31 patients $45 years old and describe several novel features associated with this age group.METHODS Patients with immunoglobulin G antibodies against the NR1 subunit of NMDAR were identified from a series of 661 cases with anti-NMDAR encephalitis.2 Detailed information on patients $45 years old, either as individual cases or age group, has not been reported previously. We used 45 years as the cutoff age because a similar threshold has been used in other autoimmune neurologic disorders, like myasthenia gravis. Clinical information was obtained by the authors or referring physicians at the acute stage of the disease.2 Follow-up information was obtained at regular intervals after symptom onset; neurologic status was assessed with the modified Rankin Scale (mRS) score. 6 Initial treatment was considered a failure if no sustained improvement occurred within 4 weeks after initiation of immunotherapy or tumor removal, and if the mRS score remained $4.2 Serum and CSF antibody studies were conducted as reported. Demographic information and symptoms were analyzed with the Fisher exact test, Fisher-Freeman-Halton test, or Mann-Whitney U test when appropriate, comparing these 31 patients with 338 recently reported patients (aged 18-44 years).

A10(EXTEM) is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10(EXTEM) of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10(EXTEM) of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen-rich products.

No abstract

TT proximalization osteotomy provides satisfactory results in improving a lack of flexion and pain in patella baja post-TKR.

Biofeedback is effective in more than 75% of patients with fecal incontinence. Clinical characteristics of patients and results of baseline tests have no predictive value of response to therapy. Specifically, we found no association between severity of electromyographic deficit and clinical response.

No abstract