Improvements in pain, medication use and quality of life in onabotulinumtoxinA-resistant chronic migraine patients following erenumab treatment - real world outcomes.

BACKGROUND: The CGRP antagonists offer a novel therapeutic approach in migraine. Their utility in patients with severe forms of chronic migraine is a subject of particular interest. We present outcomes of 9 months of erenumab treatment in a cohort of patients with difficult-to-control chronic migraine, all of whom had prior unsatisfactory response to onabotulinumtoxinA. METHODS: We offered erenumab to 98 patients with a prior unsatisfactory response to onabotulinumtoxinA. Eighty of 98 had trialled greater occipital nerve injections (82%), 32/98 peripheral neurostimulation (33%) and 18/98 intravenous dihydroergotamine (18%). Thirty eight of 98 (39%) met the definition of triptan overuse and 43/98 (44%) analgesic overuse. All patients met the EHF criteria for 'resistant migraine'. Outcome measures (recorded monthly) included days with headache limiting activities of daily living ("red"), not limiting ("amber"), headache free ("green"), and requiring triptans or other analgesics. Quality of life scores - headache impact test 6 (HIT-6), patient health questionnaire 9 (PHQ-9) and pain disability index (PDI) - were also measured. RESULTS: Mean number of red days improved by - 6.4 days (SE 0.67, 95%CI - 7.7 to - 5.1, p=0.001) at 3 months; - 6.8 days (SE 0.96, 95%CI - 8.80 to - 4.9, p=0.001) at 6 months and - 6.5 days (SE 0.86, 95%CI - 8.3 to - 4.8, p=0.001) at 9 months. Repeated measures ANOVA confirmed improvements in the number of red (p=0.001), green (p=0.001), triptan (p=0.001) and painkiller days (p=0.001) as well as scores of the HIT-6 (p=0.001), PHQ-9 (p=0.001), and PDI (p=0.001) across the duration of study. CONCLUSION: We observed improvements in pain, medication use and quality of life in onabotulinumtoxinA-resistant chronic migraine patients following erenumab treatment.

Unsaturated Cuticular Hydrocarbons Enhance Responses to Sex Pheromone in Spruce Budworm, Choristoneura fumiferana.

The primary sex pheromone components of the female spruce budworm, Choristoneura fumiferana (Clem.) (Lepidoptera: Tortricidae), are (E)- and (Z)-11-tetradecenal, produced in 95:5 ratio. However, male flight responses to calling females in a wind tunnel were faster and maintained longer than responses to any synthetic aldehyde blend. Analyses of cuticular extracts from spruce budworm adults revealed series of n-alkanes and n-monoalkenes with predominantly odd numbers of carbon atoms from C23- C29 in both sexes. (Z,Z,Z)-3,6,9-tricosatriene and (Z,Z,Z)-3,6,9-pentacosatriene were identified only in cuticular extracts from females. Pheromonally naïve males showed wing fanning and circling responses to forewing scales from females but not to scales from males. Males also exhibited the same strong responses to scales excised from pharate females, indicating that the pheromone components are produced by females prior to emergence. (Z)-11-hexadecenal and (Z)-5-tricosene enhanced male responses to the primary sex pheromone aldehydes in wind tunnel bioassays, including higher proportions of in-flight and copulatory responses by males and increased time on the source. Addition of (Z,Z,Z)-3,6,9-tricosatriene to the 95/5 blend of (E)- and (Z)-11-tetradecenal released close-range copulatory responses including abdomen curling on treated septa. We propose that the sex pheromone blend of C. fumiferana is composed of the 95/5 blend of (E)- and (Z)-11-tetradecenal as primary components, with (Z)-11-hexadecenal, (Z)-5-tricosene and (Z,Z,Z)-3,6,9-tricosatriene fulfilling secondary roles in orientation and close-range courtship.

A tale of the unexpected: Amyloidoma associated with intracerebral lymphoplasmacytic lymphoma.

Amyloidoma is a rare cause for intracranial space-occupying lesions diagnosed on brain imaging. Histology of excised tissue usually reveals the presence of a discrete, λ-light chain secreting plasmacytoma adjacent to an amyloid mass comprising aggregated monoclonal immunoglobulin light chains. We described a patient with intracerebral amyloidoma associated with a localised lymphoplasmacytic lymphoma and no systemic paraproteinaemia, tumour or amyloid deposits.

Giant cell myositis responsive to combined corticosteroids and immunoglobulin.

A 70-year-old man presented with respiratory distress and proximal muscle weakness shortly after biopsy of a left forearm mass. The biopsy showed giant cell myositis, and serological investigations identified a grossly elevated serum creatine kinase level, suggesting skeletal muscle damage. Serum troponin T was also high, but troponin I was normal. Serum antiacetylcholine receptor antibodies were positive, and imaging showed a thymoma. He recovered well following intravenous immunoglobulin and corticosteroids, and later underwent thymectomy. He is currently in sustained remission, with no clinically detectable myasthenia, but subsequently, developed hypogammaglobulinaemia. Neurologists should remember giant cell myositis/myocarditis can occur in patients who have myasthenia gravis with thymoma, as it is potentially fatal, but may respond to immunosuppression.

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Susceptibility and outcome in MS: associations with polymorphisms in pigmentation-related genes.

Multiple sclerosis (MS) risk is determined by environment and genes. The authors investigated in 419 cases and 422 controls if polymorphism in the vitamin D receptor (VDR), melanocortin-1 receptor (MC1R), and tyrosinase (TYR) genes is linked with MS risk and outcome. VDR ff was associated with reduced (odds ratio [OR] = 0.59) and MC1R His294-encoding alleles with increased (OR = 2.21) risk. MC1R Glu84/Glu84 was linked with disability (OR = 5.65). These preliminary data suggest a role for these genes in MS pathogenesis.

Does trauma trigger multiple sclerosis? 2: A medicolegal view.

Set against the scientific debate in multiple sclerosis are a number of medicolegal cases in which the scientific evidence has been examined in the context of specific events. It is instructive to understand something of the legal approach to cause and association, and to consider this in relation to individual cases.

Does trauma trigger multiple sclerosis? 1: A controversy.

The potential role of trauma in the development of multiple sclerosis is important but controversial. Patients commonly ask about this and it has important medicolegal ramifications. In addressing such issues this article will consider both physical and psychological trauma, examine pathogenic mechanisms, and discuss the evidence for and against a relationship.

HLA-DRB1 and disease outcome in multiple sclerosis.

The association between susceptibility to multiple sclerosis (MS) and the class II MHC allele HLA-DRB1*15 is well established although a possible relationship between this allele and outcome in MS is less clear. HLA-DRB1 typing was performed on 375 unrelated white patients with clinically definite MS and on 367 healthy controls. Putative associations of the gene with outcome were examined by dividing patients into two groups: those with an EDSS of 0-5.5 (mild/moderate disease) and those with an EDSS of 6-10 (severe disease). In order to minimise the effects of disease variability patients with a disease duration of at least 10 years or 15 years were examined. As subsidiary HLA-DRB1*03 and HLA-DRB1*04 associations have been previously reported, the effect of these alleles was also examined. As expected, HLA-DRB1*15 was found more frequently in patients than in controls (P < 0.000001). HLA-DRB1*15 positive patients had a significantly earlier age at onset than HLA-DRB1*15 negative patients. No significant associations were noted between HLA-DRB1*15 and outcome in the total patient group or in patients with a disease duration of 10 years or longer. In patients with a disease duration of at least 15 years HLA-DRB1*15 negative status was associated with a worse prognosis, although this did not remain significant after correction for multiple testing. It is thus likely that the contribution of HLA in MS is primarily towards onset and initial triggering mechanisms rather than influencing disease progression, chronicity and severity.

Correlation of MRI lesions with visual psychophysical deficit in secondary progressive multiple sclerosis.

The aim of this work was, first, to clarify the nature of the relationship between the sensory deficit in the demyelinated visual pathway and morphological changes revealed by MRI and, secondly, to test whether there was a preferential effect of demyelination for either the magnocellular or parvocellular pathway in established multiple sclerosis. Twenty-four patients with secondary progressive multiple sclerosis were studied psychophysically and by MRI of the optic nerve and brain. MRI was performed with a Phillips (0.5T) scanner. Visual pathway MRI lesion load was evaluated independently using the total optic nerve lesion length and lesion area seen on STIR (short inversion time inversion recovery) images of the optic nerve and the total post-chiasmal lesion area on T(1)-, T(2)- and proton-density-weighted images of the brain. Psychophysical tests determined 75%-seeing thresholds for horizontal gratings consisting of isoluminant red and green sinusoids of the same spatial frequency combined out-of-phase for preferential stimulation of the parvocellular system and in-phase for preferential stimulation of the magnocellular system. It was found that, in this group of patients, visual psychophysical loss was significantly correlated with lesion area seen on proton density MRI sequences of the post-chiasmal visual pathway, and that the parvocellular pathway was more affected than the magnocellular pathway, especially at lower spatial frequencies.