A.1 CSF Findings in Early Active Autoimmune Encephalitis

Background: Treatment decisions for patients with autoimmune encephalitis (AE) frequently need to be made before results from autoantibody testing are available, as early treatment is associated with better outcomes. Cerebrospinal fluids (CSF) white blood cell (WBC) count and protein concentration measured early on in the disease process is often used, in combination with other clinical factors, to evaluate the likelihood that a patient has AE. Methods: CSF characteristics (WBC count, protein concentration, and oligoclonal banding) measured in a first AE presentation, prior to results of autoantibodies being available, were retrospectively analyzed at two tertiary care centers. Results: Ninety-five patients were included in the study. CSF WBC counts and protein levels were within normal limits for 27% (CI95%: 19–37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6–16) of patients had “normal” CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0–544) and the median CSF protein concentration was 0.42 g/L (range: 0.15–3.92). Conclusions: A substantial proportion of patients with early active AE had a CSF WBC count or protein concentration within the normal. Inclusion of CSF oligoclonal banding may help identify a higher proportion of patients with an inflammatory CSF profile early in the disease process.

Laboratory Performance on Reporting Monoclonal Gammopathy During Cerebrospinal Fluid Oligoclonal Banding Analysis from External Quality Assessment Surveys

Objective Cerebrospinal fluid (CSF) oligoclonal banding (OCB) analysis is a sensitive test used to mainly aid multiple sclerosis (MS) diagnosis. Monoclonal gammopathy is usually an incidental finding during CSF OCB analysis. The aim of this study was to assess laboratory performance on reporting monoclonal gammopathy pattern during CSF OCB analysis based on external quality assessment surveys. Methods The CSF OCB surveys from the College of American Pathologists (CAP) from 2010 to 2015 were reviewed. The UK National External Quality Assessment Service (NEQAS) CSF OCB surveys from 2014 to 2017 were also reviewed. All monoclonal gammopathy patterns were confirmed by serum protein electrophoresis followed by immunofixation on a Sebia Hydrasys analyzer. Results There were 11 monoclonal gammopathy cases identified in the CAP OCB survey from 2010 to 2015. The average rate of CAP participants that correctly reported the pattern was 25.1% (range, 2.4%–66.7%). The most common pattern incorrectly reported was the systemic inflammation pattern, followed by the oligoclonal bands present/positive pattern. The NEQAS OCB survey from 2014 to 2017 had 4 monoclonal gammopathy cases and indicated a much higher number (average, 88.5%; range, 84.1%–90.8%) of participating laboratories to successfully detect monoclonal gammopathy. Conclusion Monoclonal gammopathy is still an underrecognized pattern in the CSF OCB analysis by the CAP participating laboratories and warrants further education.

Paediatric optic neuritis: factors leading to unfavourable outcome and relapses

ObjectivesTo identify prognostic factors associated with poor visual recovery and chronic relapsing diseases, for example, multiple sclerosis (MS), in children with optic neuritis (ON) at onset.MethodsThis multicentre retrospective study included 102 children with a first ON episode between 1990 and 2012. The primary criterion was poor visual recovery determined by visual acuity, and the secondary was relapses following ON.ResultsMedian age was 11 years, 66% were girls and mean follow-up was 24 months. 58% of children were diagnosed with idiopathic isolated ON, 22% had MS, 5% had Devic’s neuromyelitis optica and 6% chronic relapsing inflammatory ON. Complete visual acuity recovery rate was 57% (95% CI=[46%-69%]) at 6 months and 71% (95% CI=[60%-81%]) at 1 and 2 years but was lower in MS (p<0.01), with recovery rate of only 27% (95% CI=[12%-54%]) at 1 year. Age ≥10 years, optic disc pallor at funduscopy and MS were the principal factors associated with poor visual recovery. Age ≥10 years, abnormal brain MRI at onset and oligoclonal banding were significantly associated with MS (p<0.01).ConclusionAge ≥10, optic disc pallor and MS were associated with poor recovery. Better identification of these patients may help to adapt treatment and lead to a prospective treatment study.

Severe necrotizing myelopathy from toxacariasis

We present a 25 year old female veterinarian technician presenting with rapidly progressive quadriplegia in less then 12 hours. Her symptoms occurred at work with initially bilateral hand weakness followed by arm and leg weakness. Before the end of the day she was on a ventilator in the ICU. MRI showed a hyperintense longitudinal T2 signal extending from the cervical medullary junction to T1. Extensive cervical spinal cord edema with cord expansion was noted. CSF showed normal protein and cell count with no oligoclonal banding. A post-infectious inflammatory process causing transverse myelitis was presumed and she was given IVIG, steroids, and plasmapheresis with no improvement. A serum ELISA test for IgG to Toxocara was reactive at titre of 1:800 at 3 weeks after her initial presentation. Her serum IgE levels was elevated at 169 x 10x3 U/L (Normal <87 x 10x3 U/L). At 4 weeks, she was commenced on albendazole at 800 mg per day for two months. A repeat serum ELISA test at 6 weeks and 2 weeks into her treatment with albendazole showed a declining titre of 1:200 consistent with recent Toxocara infection. At 10 weeks, her ELISA test was non-reactive. Unfortunately she did not respond to albendazole treatment and she shows minimal improvement now 1.5 years later.

The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude

Background: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) statusfor the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. Methods: In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. Results: A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude ( p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change ( p < 0.001). Conclusions: The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.