Remyelination efficiency declines with advancing age in animal models, but this has been harder to demonstrate in people with multiple sclerosis. We show that bexarotene, a putatively remyelinating retinoid-X receptor agonist, shortened the visual evoked potential latency in patients with chronic optic neuropathy aged under 42 years only (with the effect diminishing by 0.45 ms per year of age); and increased the magnetization transfer ratio of deep gray matter lesions in those under 43 years only. Addressing this age-related decline in human remyelination capacity will be an important step in the development of remyelinating therapies that work across the lifespan.

Introduction There is growing interest in the prediction of incident atrial fibrillation (AF). The 12-lead electrocardiogram (ECG) has been a particularly rich target for possible prediction strategies. Purpose The P-wave axis is an ECG parameter that reflects the dominant vector of atrial depolarisation and is usually 0° -75°. There is a large body of literature suggesting that AF reflects structural and conduction abnormalities of the atria, and thus the P-wave axis may represent a sensitive parameter to detect such changes. Methods A systematic review and meta-analysis of published literature associating abnormal P-wave axis and the development of incident AF was performed. Electronic databases were systematically searched from inception to October 2021. A random-effects model with generic inverse variance weights was utilised to pool the most adjusted effect measure from each paper. A funnel plot was used to assess publication bias. Results After excluding duplicate studies, 568 studies were screened. A total of eleven studies were identified that associated an abnormal P-wave axis with the subsequent detection of AF. The eight studies that considered abnormal P-wave axis as being <0° or >75° were pooled for meta-analysis. In the pooled studies a total of 78,222 patients were included with 5656 cases of incident atrial fibrillation identified. The meta-analysis of the studies suggested that an abnormal P-wave axis was associated with a pooled risk ratio of 2.12 (95% CI 1.49 to 3.01) for the detection of incident atrial fibrillation. Conclusion This comprehensive systematic review and meta-analysis, indicates the positive association of abnormal P wave axis and future detection of AF. Utilisation of abnormal P-wave axis, alongside other parameters, may allow clinicians to better risk-stratify individuals at increased risk of AF, and thus identify those who may benefit most from prolonged cardiac monitoring or targeted anticoagulation.

An 18-year-old female presented with rapidly progressive ascending flaccid paralysis, respiratory failure and bilateral VI and VII cranial nerve palsies. She was diagnosed with Guillain-Barré syndrome (GBS) and, following intravenous immunoglobulin (IVIG) and plasma exchange (PLEX), made steady improvement. Seventy-four days after presentation and despite continued clear improvement in her other symptoms, she developed headaches, bilateral optic disc swelling and a dilated, tonic left pupil with light-near dissocia- tion. Her cerebrospinal fluid (CSF) protein was markedly elevated. She was managed with serial lumbar punctures and steroids and had an excellent response. Optic disc swelling is an unusual but described complication of GBS and may be caused by raised intracranial pressure, disorders of CSF protein (or its resorption) or direct inflammation of the optic nerve itself. Prompt recognition and appropriate manage- ment are essential to avoid permanent visual loss. We discuss differential diagnosis and management of this challenging clinical entity of delayed onset of optic disc swelling and very elevated CSF protein in the context of acute inflammatory neuropathy.

Remyelination is a promising strategy to prevent axonal degeneration and progressive disability in people with multiple sclerosis (MS). In animal models, remyelination becomes inefficient with advancing age and much preclinical research is focused on interventions to reverse cellular hallmarks of ageing in remyelinat- ing lesions. However, there is currently limited evidence that human remyelination also declines with age.We investigated the effect of patient age on treatment response among participants of the CCMR One trial (ISRCTN14265371): a double-blind, placebo-controlled phase 2a study (n=52) that demonstrated the ability of bexarotene, a retinoid-X receptor agonist, to promote remyelination in people aged 25–50 with relapsing remitting MS. For eyes with chronic optic neuropathy (baseline latency >118ms), bexarotene shortened the full-field visual-evoked potential P100 latency maximally in younger patients. The treatment effect diminished by approximately 0.5ms per year, such that older patients receiving bexarotene had a similar P100 latency change to controls. Furthermore, MRI scans of the same patients demonstrated an age-dependent treatment effect on lesion magnetisation transfer ratio, a radiological correlate of remyelination.These results provide evidence that bexarotene promotes remyelination best in younger patients, rein- forcing the need to address the age-associated decline in remyelination capacity to develop successful remyelinating therapies.cem73@cam.ac.uk|NIHR Bursary