Enhancing departmental teaching in the digital age: as easy as 1-3-5.

We have recently introduced a new item to our neurology Grand Rounds-the '1-3-5 presentation'. The format comprises a presentation on one topic, using three slides and lasting no more than 5 minutes. This a useful way of covering brief single topics and introducing and sparking discussion on more complex ones. '1-3-5s' have proven popular in our department and we have compiled a library of these presentations that is hosted on a YouTube channel. This article discusses the benefits and prospects for this format and encourages other units to provide similar opportunities for teaching and learning among all clinical grades.

Rim lesions are demonstrated in early relapsing-remitting multiple sclerosis using 3 T-based susceptibility-weighted imaging in a multi-institutional setting.

PURPOSE: Rim lesions, characterised by a paramagnetic rim on susceptibility-based MRI, have been suggested to reflect chronic inflammatory demyelination in multiple sclerosis (MS) patients. Here, we assess, through susceptibility-weighted imaging (SWI), the prevalence, longitudinal volume evolution and clinical associations of rim lesions in subjects with early relapsing-remitting MS (RRMS). METHODS: Subjects (n = 44) with recently diagnosed RRMS underwent 3 T MRI at baseline (M0) and 1 year (M12) as part of a multi-centre study. SWI was acquired at M12 using a 3D segmented gradient-echo echo-planar imaging sequence. Rim lesions identified on SWI were manually segmented on FLAIR images at both time points for volumetric analysis. RESULTS: Twelve subjects (27%) had at least one rim lesion at M12. A linear mixed-effects model, with 'subject' as a random factor, revealed mixed evidence for the difference in longitudinal volume change between rim lesions and non-rim lesions (p = 0.0350 and p = 0.0556 for subjects with and without rim lesions, respectively). All 25 rim lesions identified showed T1-weighted hypointense signal. Subjects with and without rim lesions did not differ significantly with respect to age, disease duration or clinical measures of disability (p > 0.05). CONCLUSION: We demonstrate that rim lesions are detectable in early-stage RRMS on 3 T MRI across multiple centres, although their relationship to lesion enlargement is equivocal in this small cohort. Identification of SWI rims was subjective. Agreed criteria for defining rim lesions and their further validation as a biomarker of chronic inflammation are required for translation of SWI into routine MS clinical practice.

Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case-control studies.

OBJECTIVE: Neurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case-control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other. METHODS: Guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and 'grey' literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis. RESULTS: CSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001). CONCLUSIONS: CSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease 'activity' rather than as a marker of disability or disease stage.

Wound botulism, its neurological manifestations, treatment and outcomes: A case series from the Glasgow outbreak, 2015.

Background and aims We examined the neurological manifestations, treatment and outcomes of a subset of 25 patients within the largest ever outbreak of wound botulism in Europe. Methods and results All 25 cases were intravenous drug users. The most common presenting symptom was dysarthria in 19/25 (76%), followed by dysphagia in 12/25 (48%), blurred vision in 10/25 (40%) and double vision in 8/25 (32%). Microbiological analysis confirmed the diagnosis in nine cases (36%). Duration of admission positively correlated with time to antitoxin, time to wound debridement and female sex. Conclusion As the outbreak continued, hospital stays shortened, reflecting growing awareness of the outbreak and quicker treatment initiation.

A treatable inborn error of metabolism presenting in the sixth decade.

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. If untreated, PKU can result in global developmental delay, learning difficulties or seizures. For that reason, PKU is included in the UK neonatal screening programme. We describe a patient in his sixth decade presenting with progressive cognitive decline and spasticity, in whom a diagnosis of PKU was eventually reached. We note that although we currently have a robust neonatal screening programme, this has not always been the case. Patients born before 1969 were not screened, and tests used in early screening programmes were less sensitive than those used today. This case serves as a reminder that inherited metabolic disorders may present in later life and may mimic the neurocognitive and radiological picture of other white matter syndromes.

Multiple sclerosis and exercise-A disease-modifying intervention of mice or men?

Research suggests that physical exercise can promote an anti-inflammatory and neuroprotective state. If so, increasing or optimizing exercise could be considered a 'disease-modifying intervention' in neuroinflammatory diseases, such as multiple sclerosis (MS). Exercise intervention studies conducted in animal models of MS are promising. Various aerobic and strength training regimes have been shown to delay disease onset and to reduce both the clinical and pathological disease severity in mice. However, fundamental differences between the physiology of animals and humans, the disease states studied, and the timing of exercise intervention are significant. In animal models of MS, most exercise interventions begin before disease initiation and before any clinical sign of disease. In contrast, studies in humans recruit participants on average nearly a decade after diagnosis and often once disability is established. If, as is thought to be the case for disease-modifying treatments, the immunomodulatory effect of exercise decreases with advancing disease duration, current studies may therefore fail to detect the true disease-modifying potential. Clinical studies in early disease cohorts are needed to determine the role of exercise as a disease-modifying intervention for people with MS.

Longitudinal retinal imaging study of newly diagnosed relapsing-remitting multiple sclerosis in Scottish population: baseline and 12 months follow-up profile of FutureMS retinal imaging cohort.

OBJECTIVE: Multiple sclerosis (MS) is an inflammatory degenerative condition of central nervous system. The disease course and presentation of MS is highly heterogeneous. Advanced retinal imaging techniques such as optic coherence tomography (OCT) can capture abnormalities of anterior visual pathway with high resolution, which may contribute greater insights into the pathophysiology of MS. METHODS: People with newly diagnosed relapsing-remitting MS were recruited for FutureMS retinal imaging study from two study centres in Scotland. The baseline visit was completed within 6 months of diagnosis with initial follow-up 12 months after the baseline visit. The assessments included in FutureMS retinal imaging study were visual acuity test, self-reported eye questionnaire and OCT scan. RESULTS: A total of 196 FutureMS participants completed the retinal imaging study of FutureMS with 185 participants at M0 and 155 at M12. A total of 144 participants completed both M0 and M12 visits. At the whole cohort level, the distribution of retinal measures is generally consistent between baseline and follow-up. CONCLUSION: The FutureMS retinal imaging study aims to demonstrate that patient with MS present with different extent of retinal abnormalities that can be captured by retinal imaging modalities such as OCT soon after diagnosis. These changes may sensitively mirror the brain atrophy or serve as predictors for disease activity. By developing sensitive, quantifiable and objective retinal biomarkers, FutureMS retinal imaging study will provide an opportunity to stratify patient with MS at an early stage and support future therapeutic strategies for a better outcome.

MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis.

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single-molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation and neurite orientation dispersion and density imaging diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 versus 0.57, difference 0.036, 95% CI: 0.029-0.043, P < 0.001). Lesion volume (Spearman's rho rs= 0.38, P < 0.001) and g-ratio (rs= 0.24, P < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) [11/23 (48%) versus 2/15 (13%), P < 0.05]. These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity and help to identify individuals with a high degree of axonal damage at disease onset.

Multiple simultaneous infections in a patient with well-controlled HIV: when Occam's razor fails.

Multiple concurrent infectious processes have previously been reported in the context of advanced HIV with significant immunosuppression. Here we report a case of multiple infections in a 56-year-old man with well-controlled HIV diagnosed 5 years earlier. Soon after returning to Australia following 12 years living in Thailand, he became unwell with fevers, night sweats, arthralgia and myalgia. There were no localising symptoms and examination was unremarkable. Investigations revealed positive syphilis (Treponema pallidum) serology with an RPR of 16, a positive urine culture (Klebsiella pneumoniae), a pulmonary nodule, a liver abscess and colitis (Entamoeba histolytica). Recovery was only complete when all the individual infections were treated.