Adrian Pace

PO141 Audit of the first line oral disease modifying treatments in greater manchester

In 2014, teriflunomide and dimethyl fumarate were approved by NHS regulators as first-line oral treatments for multiple sclerosis in England. We audited the safety, tolerability and treatment retention rates of the first line oral DMTs in Greater Manchester. Case notes of MS patients treated with first line oral DMTs were analysed for drug discontinuation reason, blood monitoring compliance and drug related side effects within the first 12 months of treatment. Of 39 patients, treated with teriflunomide, 89% were still on treatment at 12 months and reported very few side effects. 5% withdrew from treatment due to non-adherence with blood test monitoring, 3% due to lack of efficacy and 3% due to side effects. 273 patients treated with dimethyl fumarate, had a retention rate of 75% after 12 months. 12% discontinued treatment due to gastrointestinal side effects and 3% due to fatigue, headache and depression. Occasionally patients reported appetite/weight changes and altered hair appearances. 6% of patients were non-adherent with blood test monitoring. Lymphocyte drop below 0.5 for more than 3 months occurred in 2%, hence treatment was discontinued. Patient retention rate was better with teriflunomide than with dimethyl fumarate. Teriflunomide blood monitoring carries a significant administrative burden but it seems to be well tolerated in our cohort.

TUMEFACTIVE REBOUND OF MULTIPLE SCLEROSIS FOLLOWING CESSATION OF FINGOLIMOD

Fingolimod is an oral sphingosine-1-phosphate receptor modulator approved for the treatment of active relapsing remitting multiple sclerosis (RRMS). Recent reports have highlighted the possible risk of rebound disease activity after withdrawal of fingolimod. We describe a patient who developed severe tumefactive MS on discontinuing fingolimod treatment. A 32-year old female with RRMS with ongoing relapses escalated treatment from interferon-beta to fingolimod. Pre-treatment, she was JC-virus positive with high titers of 2.41. She developed side effects and persistent lymphopenia. Fingolimod was reduced to alternate day dose. She then complained of worsening memory and cognition, raising concern of PML. MRI with contrast showed ongoing MS disease activity, but no sign of PML. We planned to switch her to alemtuzumab. She discontinued fingolimod in May 2015. By July all side effects resolved. She started low dose naltrexone therapy and now declined alemtuzumab. In August she presented acutely with tetraparesis, swallowing, balance and memory difficulties. MRI images demonstrated severe rebound inflammatory disease with numerous contrast-enhancing tumefactive lesions. She was treated with intravenous steroids and alemtuzumab leading to partial neurological recovery after 6 months. Rebound MS disease following discontinuation of fingolimod presumably reflects the cessation of autoreactive lymphocyte sequestration in peripheral lymph nodes after drug washout. Early replacement with alternative immunomodulatory agents should be planned to minimize the risk of this serious complication.

THE WIDENING SPECTRUM OF PARANEOPLASTIC DISORDERS: TWO CASES

Paraneoplastic neurological syndromes are non-metastatic disorders triggered by an altered immune response to a neoplasm. Uncommon presentations are increasingly reported, widening the recognised spectrum of these disorders. We present two patients with atypical neurological manifestations that heralded malignancy. Case 1 A 79 year old woman presented with progressive asymmetrical (R>L) leg weakness. Examination confirmed significant paraparesis (MRC 2/5 bilaterally) with normal muscle bulk and tone, normal sensation and sphincter control, hyporeflexia and downgoing plantars. MRI of the lumbosacral spine was normal. Nerve conduction studies showed an axonal and demyelinating motor neuropathy. CSF was acellular with high protein (2.5 gr/dl) and normal glucose. Body CT revealed a large retrosternal mass consistent with thymoma. Her paraneoplastic motor neuropathy was treated with intravenous immunoglobulin, which clinically stabilised her progression, and referred for surgical removal. Case 2 A 72 year old woman presented with painless, progressive left-sided visual loss. Fundoscopy excluded arterial occlusion or vasculitis. Investigations for autoimmune or infective causes were normal. Chest X-ray, echocardiogram, lumbar puncture and a temporal artery biopsy were diagnostically non-contributory. Body CT showed multiple lytic and sclerotic bone lesions, with abnormal lymphadenopathy in the left axilla. Fine needle aspiration of a node showed adenocarcinoma consistent with metastatic oestrogen receptor positive breast cancer. The final diagnosis was non-metastatic paraneoplastic optic neuropathy.

AN ASSESSMENT TOOL FOR MEASURING EFFICACY OF IVIG IN CIDP

Background Intravenous immunoglobulin is a first line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). ABN guidelines have highlighted the need for evidence of IVIg efficacy in pwCIDP using validated instruments. Aim 1) To evaluate evidence on CIDP efficacy collected on pwCIDP admitted to the Royal Devon and Exeter Hospital for IVIg. 2) Based on (1), to develop an assessment tool for measuring the efficacy of IVIg therapy in pwCIDP. Methods 1) Retrospective evaluation of data from admissions to the RD&E (January-June 2013). 2) Identification of candidate validated instruments in CIDP, scale development and prospective application. Results Clinical entries (N=24) proved widely variable and generally poor (33% no neurological assessment; 29% individual muscle scores available; 39% generic comments only). We subsequently developed a composite of CIDP scales addressing strength (34-item MRC summed score), sensation (INCAT sensory summed score) and activity limitations (Overall Neuropathy Limitations Scale), applying it prospectively (August-December 2013). Analysis of the dataset (N=11) suggests a wide degree of involvement for each variable (mean MRC summed score 127/170, SD 41; mean INCAT score 13/64, SD 17; mean ONLS 5.2/12, SD 2.8) in this small cohort. Conclusion Our assessment tool captures relevant aspects of disease impact in pwCIDP and may help support responsible use of IVIg and disease monitoring.

PONM01 Measurement of global strength: stable concept, fluid ruler

Background We previously described the construction of a measure for global strength in MS. However, loss of strength is common to many diseases. Thus, a generic strength measure may prove widely applicable and allow inter-disease comparison. Aim To determine whether measurement performance of the MS-derived strength scale remained stable in people with CIDP. Method MRC strength data from the RMC study (n=238) were amalgamated with those from our previously described MS sample (n=371). Items included were the eight pairs of muscles (four upper limb; four lower limb) consistent across both studies. Rasch analysis was used to determine the extent to which the 16-item scale met expected criteria for measurement. Results Analysis indicated muscles mapped a measurable range of global strength. However, 9/16 muscles had statistically significant differential item functioning (DIF). In these muscles, mean scores in groups of equally strong people varied between diseases by up to 2.8 MRC grades. Analysing disease-specific data separately suggested muscle locations on the “strength ruler” changed in hierarchy depending on the disease measured. Conclusion Summed strength scores should not be compared across diseases. Rather, scores for different diseases should be analysed in the context of their own muscle hierarchies using a vehicle such as Rasch analysis. However, this study does identify a group of nondiscriminatory muscles on which a generic strength scale may be constructed.

PONM02 Grading strength in manual muscle testing: bespoke works better

Background The MRC 0–5 grading system is ubiquitously used to measure muscle strength. However, its criterion status is undermined by insensitivity of grades 4 and 5, which reduce its ability to detect change. Aim To test the measurement properties of an expanded MRC strength scale. Method We divided MRC grade 4 into three distinct grades, obtaining an 8-grade scale. We scored 53 muscles (25 pairs of limb muscles; three trunk muscles) in 250 people with multiple sclerosis (EDSS 0–9.0; median 6.0) on both original and expanded MRC grades. Data were analysed using the Rasch measurement model. Results Rasch analysis revealed that in 52 (original 5-grade version) and 53 (expanded 8-grade version) muscles, the grading system did not work as intended. However, grades 0–3 were largely unendorsed, despite high median disability. Uniformly rescoring these four grades as one grade rectified the problem in 52 muscles (original version), but only in 15 on the expanded version. Individualised muscle grade scoring suggested different muscles operate best with different numbers of grades. Conclusion In principle, a uniform muscle grading system is attractive. In practice, bespoke grading works better, possibly because of muscle diversity. Furthermore, MRC grades 1–3, while useful in some disorders, appear less relevant in MS.