Gavin Giovannoni

Probiotics survey is inconclusive

As promised the following are the recent result from the probiotics survey.

Forms response chart. Question title: Are you taking a probiotic?. Number of responses: 44 responses.

Forms response chart. Question title: Who recommended the probiotic?. Number of responses: 16 responses.

Forms response chart. Question title: How effective have probiotics been in helping your MS?. Number of responses: 15 responses.

I think there are too few respondents to make any judgement on this data. Probiotics and microbiome are clearly hot topics and hence we will at some stage need to generate good evidence to make some sensible recommendations to pwMS. At the moment I don’t think there is enough evidence to recommend pwMS take probiotics. I would suggest using the money you save on purchasing probiotics on doing exercise; at least for exercise, we have an emerging MS database showing that it works.

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.

Survey Disclaimer: No personal identifiers will be collected as part of these surveys unless otherwise stated. By completing these surveys you are consenting to the data you provide being analysed by Professor Giovannoni and his collaborators. Res

Are you a potential faller?

Barts-MS rose-tinted-odometer: ★★ (A Green & Yellow Friday – Lime Green (#32CC32) & Lemon Glacier (#F4FF00))

The biggest risk of losing your independence is falling and long bone fractures of the lower limbs. PwMS are 6x more likely than the general population to fall and fracture a lower limb long bone. I currently have a patient of mine with PPMS in hospital with bilateral fractures of the femur. She will not walk again.

In our experience, the best predictor of falling is the need for a walking aid. The study below shows that fallers are more likely to have progressive or advanced MS and are already less mobile.

Please, please, please if you are tripping, having near falls or have fallen please get yourself referred to a falls prevention clinic and to see a physiotherapist. There are a lot of things that can be done to prevent falls.

Another issue is bone health. Faller or near fallers need to have their bone density checked and treated if low. The majority of pwMS have osteopenia and need to be on medication to manage this problem. The reason why pwMS have thin bones is well known; less vitamin D, less sunlight, less physical activity, higher rate of smoking, intermittent steroids, etc.

Prevention of falls and fractures is better than treating their consequences. I will do a separate MS-Selfie Newsletter on falls prevention.

Block et al. Identifying falls remotely in people with multiple sclerosis. J Neurol. 2021 Aug 17;1-10. doi: 10.1007/s00415-021-10743-y.

Background: Falling is common in people with multiple sclerosis (MS) but tends to be under-ascertained and under-treated.

Objective: To evaluate fall risk in people with MS.

Methods: Ninety-four people with MS, able to walk > 2 min with or without an assistive device (Expanded Disability Status Scale (EDSS ≤ 6.5) were recruited. Clinic-based measures were recorded at baseline and 1 year. Patient-reported outcomes (PROs), including a fall survey and the MS Walking Scale (MSWS-12), were completed at baseline, 1.5, 3, 6, 9, and 12 months. Average daily step counts (STEPS) were recorded using a wrist-worn accelerometer.

Results: 50/94 participants (53.2%) reported falling at least once. Only 56% of participants who reported a fall on research questionnaires had medical-record documented falls. Fallers had greater disability [median EDSS 5.5 (IQR 4.0-6.0) versus 2.5 (IQR 1.5-4.0), p < 0.001], were more likely to have progressive MS (p = 0.003), and took fewer STEPS (mean difference – 1,979, p = 0.007) than Non-Fallers. Stepwise regression revealed MSWS-12 as a major predictor of future falls.

Conclusions: Falling is common in people with MS, under-reported, and under-ascertained by neurologists in clinic. Multimodal fall screening in clinic and remotely may help improve patient care by identifying those at greatest risk, allowing for timely intervention and referral to specialized physical rehabilitation.

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How demyelinated are my MS lesions?

Barts-MS rose-tinted-odometer: ★★★★★ (Vermillion Monday code #E34234)

There are very few what I call really deep-thinkers in MS research and Danny Reich is one of them. This paper from his group is so simple in its inception and execution; it is a fine example of seeing the woods for the trees. They use a relatively simple MRI technique to interrogate MS lesions to classify them as being remyelinated, demyelinated or mixed.

Using an MRI sequence they classify MS brains lesions as being “long-T1,” “short-T1,” and “mixed-T1”, which correspond to fully demyelinated, fully remyelinated, and mixed demyelinated/remyelinated lesions, respectively. Neat? You bet it is neat. Demyelination, rather than axon loss, dominantly contributed to initial T1 prolongation, which is a metric from the TI relaxation time* on imaging.

*T1 is the so-called longitudinal relaxation time and is the time constant that determines the rate at which excited protons return to equilibrium. It is a measure of the time taken for spinning protons to realign with the external magnetic field.

Short-T1 or remyelinated lesions were most common in the deep white matter, whereas long-T1/demyelinated and mixed-T1/demyelinated-remyelinated lesions were more common in lesions next to the cortex (juxtacortical) and ventricles (periventricular) and were much more likely to have paramagnetic or iron rims suggesting chronic inflammation. The latter are the so-called slowly expanding lesions that are one of the drivers of smouldering MS.

Please note older age at the time of lesion formation meant less remyelination, which is another reminder that as you get older your recovery mechanisms fail.

The question is whether or not this simple technique can be used as an outcome measure in trials and/or to profile pwMS for remyelination studies. There is little reason to load remyelination trials with patients who are not going to be able to respond to remyelination treatments. What about using this technique as a prognostic tool? Is there a biological reason, apart from age, why some pwMS remyelinate and others don’t?

Could this technique be used to supplement evoked potentials to assess whether or not a condition is demyelinating, i.e. as an aid to help make a diagnosis of MS?

You know a paper is good when it leaves you asking more questions than it answers.

Kolb et al. 7T MRI Differetiates Remyelinated from Demyelinated Multiple Sclerosis Lesions. Ann Neurol. 2021 Aug 14.

Objective: To noninvasively assess myelin status in chronic white matter lesions of multiple sclerosis (MS), we developed and evaluated a simple classification scheme based on T1 relaxation time maps derived from 7-tesla postmortem and in vivo MRI.

Methods: Using the MP2RAGE MRI sequence, we classified 36 lesions from 4 postmortem MS brains as “long-T1,” “short-T1,” and “mixed-T1” by visual comparison to neocortex. Within these groups, we compared T1 times to histologically derived measures of myelin and axons. We performed similar analysis of 235 chronic lesions with known date of onset in 25 MS cases in vivo and in a validation cohort of 222 lesions from 66 MS cases, investigating associations with clinical and radiological outcomes.

Results: Postmortem, lesions classified qualitatively as long-T1, short-T1, and mixed-T1 corresponded to fully demyelinated, fully remyelinated, and mixed demyelinated/remyelinated lesions, respectively (p ≤ 0.001). Demyelination (rather than axon loss) dominantly contributed to initial T1 prolongation. We observed lesions with similar characteristics in vivo, allowing manual classification with substantial interrater and excellent intrarater reliability. Short-T1 lesions were most common in the deep white matter, whereas long-T1 and mixed-T1 lesions were prevalent in the juxtacortical and periventricular white matter (p = 0.02) and were much more likely to have paramagnetic rims suggesting chronic inflammation (p < 0.001). Older age at the time of lesion formation portended less remyelination (p = 0.007).

Interpretation: 7-tesla T1 mapping with MP2RAGE, a clinically available MRI method, allows qualitative and quantitative classification of chronic MS lesions according to myelin content, rendering straightforward the tracking of lesional myelination changes over time.

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Probiotics: yes, no or maybe?

Barts-MS rose-tinted-odometer: ★★ (Black Friday, Friday the 13th #000000)

The meta-analysis below of probiotics suggests they may help people with MS (pwMS). However, when you drill down into the details you will note that there were only four studies included in the meta-analysis with 213 actively treated subjects compared to 107 controls. Far too small to be confident of an effect. The problem with probiotics is not only their definition but trying to work out what they actually do in terms of MS pathology. The rationale for prescribing probiotics to treat MS is based on the potential for gut bacteria to be anti-inflammatory and to stimulate regulatory cells. This hypothesis is based largely on animal studies and I am yet to be convinced it has any relevance to multiple sclerosis. This is why I don’t recommend probiotics to my patients. If your financial resources are limited I would question spending them on unproven therapies such as probiotics.

I would be interested to know how many of you are taking probiotics, who prescribed them and have you noticed any effect?

Mirashrafi et al. Effect of Probiotics Supplementation on Disease Progression, Depression, General Health and Anthropometric Measurements in Relapsing-Remitting Multiple Sclerosis Patients: A Systematic Review and Meta-analysis of Clinical Trials. Meta-Analysis Int J Clin Pract. 2021 Aug 11;e14724.

Methods: The English literature search was performed using PubMed, Scopus, Web of Science, and the Central Cochrane Library through January 2021. Random effect models were used to synthesize quantitative data by STATA14 .

Results: From a total of 152 identified entries, four trials were included in quantitative synthesis (n=213; 106 as intervention, 107 as control). An additional six studies with the same structure and different markers were also systematically reviewed. The pooled effect size showed that Expanded Disability Status Scale (EDSS) (WMD=-0.43; 95% CI=-0.65, -0.20; P<0.001), Beck Depression Inventory-Ⅱ (BDI-Ⅱ) (WMD=-3.22; 95% CI=-4.38, -2.06; P<0.001) and General Health Questionnaire (GHQ) (WMD=-4.37; 95% CI=-6.43, -2.31; P<0.001) were improved following probiotics supplementation. However, body weight and body mass index did not statistically change.

Conclusion: Our findings revealed that probiotics supplementation can improve disease progression, suppress depression, and general health in MS patients; although, further investigations may be needed.

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How important is your brain volume?

Barts-MS rose-tinted-odometer: ★★★★★ (A blue sky and sunflower yellow Tuesday; #87CEEB #ffda03)

I bang on about treating-2-target beyond NEIDA (no evident inflammatory disease activity) and targeting the end-organ, i.e. to try and normalise brain volume loss (BVL). The aim is to get pwMS to old age with a healthy brain so that they can age normally. Who wants to be at risk of premature ageing and being demented earlier than you have to be?

When it comes to BVL, not all DMTs are made equal. At the top of the ladder are HSCT and alemtuzumab, then natalizumab. Behind these come the anti-CD20 therapies, the S1P modulators, cladribine, teriflunomide and the also-rans.

In the smallish real-life study below pwMS who have been on natalizumab for at least 2 years appear to lose brain volume at a similar rate as normal controls. I wonder what would happen over a longer period of time? Natalizumab is very effective but it does not necessarily get on top of smouldering MS, so some patients will be doing better than others. Don’t be lulled into a sense of security by the average effect; 50% of people do worse than average (median) and 50% of people do better than average (median).

Please be aware that BVL is complicated with many physiological (day-2-day), biological (age), disease factors(duration, level of disability, lesion load, comorbidities) and other Influences (e.g. genomic factors) affecting the brain volume and rate of BVL. Despite BVL not being assessed in routine clinical practice, it is one of the metrics that need to be taken into account when choosing your DMT. Just maybe BVL should be the most important factor to consider in terms of efficacy? What do you think?

Yes, the volume of your brain predicts disability outcomes, cognition and how well you will do in old age.

Alvarez et al. Brain atrophy rates in patients with multiple sclerosis on long term natalizumab resembles healthy controls. Mult Scler Relat Disord. 2021 Jul 24;55:103170.

Background: Clinically stable multiple sclerosis (MS) patients often have negligible inflammatory MRI changes. Brain atrophy may provide insight into subclinical disease progression. The objective was to compare brain atrophy rates in stable patients on long term natalizumab treatment vs. age and gender matched healthy non-MS controls (HC) prospectively over two-years examining brain volume, cognition, and patient reported outcomes (PROs).

Methods: MS patients treated with natalizumab for a minimum of 2 years, age 18-60 were recruited and compared with age- and gender-matched healthy controls (HC). Both groups were followed prospectively to obtain two years of consecutive magnetic resonance imaging, clinical and PRO data. Baseline normalized brain volume (NBV), yearly T2 lesion volume (T2LV), and percent brain volume change (PBVC) were measured using SIENAX, JIM 6.0, and SIENA respectively. Neuropsychological tests from the MACFIMS battery were selected to optimize assessments for impairments in the domains of information processing speed and memory. Patient reported outcomes (PROs) for domains of physical, mental and social quality of life were evaluated using the NeuroQol short forms.

Results: Forty-eight natalizumab and 62 HC completed all study visits. At baseline, unadjusted mean NBV (natalizumab=1508.80cm (Popescu et al., 2013) vs. HC=1539.23cm (Popescu et al., 2013); p=0.033) and median baseline T2LV (natalizumab=1724.62mm (Popescu et al., 2013) vs. HC=44.20mm (Popescu et al., 2013); p=<0.0001) were different. The mean PBVC at year 2, adjusted for gender and baseline age was -0.57% (CI: 0.7620, -0.3716) for natalizumab and -0.50% (-0.7208, -0.2831) for HC, but the difference between groups was not statistically significant (0.073%; p=0.62). Over the 2-year period, HC demonstrated mild improvements in some cognitive tests vs. natalizumab subjects. However, PROs were similar between the two groups.

Conclusion: Stable MS patients on natalizumab have similar brain volume loss as people who do not have MS, suggesting normalization of brain atrophy.

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MS at the limits 2021

Are you an HCP working in MS? These two meetings – yes they are face-2-face – may interest you. The feedback from the previous three meetings has been the best feedback I have ever seen for an academic MS meeting. More than 98% of attendees said they would definitely attend again, 100% of attendees said they would recommend it to colleagues and friends and the majority said they preferred the meetings to the large international meetings because of the intimate format of the meetings and the fact that there is a lot of time for discussion. As with so many things in life, less usually means more. If I can say so myself the programmes look very exciting and a time to look beyond COVID-19.

Please register online; HCPs and MS Nurses.

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Are you feeling prematurely old?

Barts-MS rose-tinted-odometer: ★★ (Gray Thursday as in getting old Thursday #808080)

As you are all aware ageing is a fact of life and is essential for evolution to do its job properly. Even bacteria and fungi age. Ageing is, therefore, a biological process and is driven by various biological pathways and networks controlled by our genes. It is well known that chronic inflammation results in accelerated ageing and there is a hypothesis that multiple sclerosis (MS) causes premature ageing and is one of the drivers of smouldering or non-relapsing progressive MS.

One of the biological markers of ageing is the length of your chromosomes. As cells divide, the end of the chromosomes or telomeres shorten. The length of the telomeres can be used as a biological clock of ageing. The review below of 7 studies in pwMS shows that pwMS have shorter telomeres than controls; in other words, they are biologically older than healthy age-matched controls.

Shorter telomeres, i.e. premature ageing, in pwMS is associated, independently of age, with greater disability, lower brain volume (end-organ damage), increased relapse rate and more rapid conversion from relapsing to progressive MS.

So is there anything you can do about the ageing process? Yes, make sure you are NEIDA (no evident inflammatory disease activity) and that you are doing everything you can from a health and wellness perspective, which are the only antiageing strategies at our disposal.

I am seeing an increasing number of older people with MS, i.e. 50+ years of age, who are developing progressive worsening of their functioning after many years of being NEIDA on a DMT and stable physically. When I interrogate these patients clinically, radiologically with MRI and biochemically (spinal fluid analysis) I can’t find any evidence of MS disease activity. I simply say these people have smouldering MS, but I suspect a large part of what we are seeing is age-related neurodegeneration that is occurring decades early than it should because MS has shredded their brain and cognitive reserve. The only solution to this problem is early diagnosis and treatment upfront with the aim of protecting the reserve capacity of the nervous system so pwMS can age normally. The latter is why we launched our “MS Brain Health: Time Matters” initiative to address this problem.

Please let me know what you are doing to protect your brain and cognitive reserve? Do you feel prematurely old? What advice do you have for the next generation of pwMS?

Bühring et al. Systematic Review of Studies on Telomere Length in Patients with Multiple Sclerosis. Aging Dis. 2021 Aug 1;12(5):1272-1286.

Telomeres are protective cap structures at the end of chromosomes that are essential for maintaining genomic stability. Accelerated telomere shortening is related to premature cellular senescence. Shortened telomere lengths (TL) have been implicated in the pathogenesis of various chronic immune-mediated and neurological diseases. We aimed to systematically review the current literature on the association of TL as a measure of biological age and multiple sclerosis (MS). A comprehensive literature search was conducted to identify original studies that presented data on TL in samples from persons with MS. Quantitative and qualitative information was extracted from the articles to summarize and compare the studies. A total of 51 articles were screened, and 7 of them were included in this review. In 6 studies, average TL were analyzed in peripheral blood cells, whereas in one study, bone marrow-derived cells were used. Four of the studies reported significantly shorter leukocyte TL in at least one MS subtype in comparison to healthy controls (p=0.003 in meta-analysis). Shorter telomeres in patients with MS were found to be associated, independently of age, with greater disability, lower brain volume, increased relapse rate and more rapid conversion from relapsing to progressive MS. However, it remains unclear how telomere attrition in MS may be linked to oxidative stress, inflammation and age-related disease processes. Despite few studies in this field, there is substantial evidence on the association of TL and MS. Variability in TL appears to reflect heterogeneity in clinical presentation and course. Further investigations in large and well-characterized cohorts are warranted. More detailed studies on TL of individual chromosomes in specific cell types may help to gain new insights into the

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Does MS exile you from the everyday of life?

Barts-MS rose-tinted-odometer: ★★★★★ (Sunday or Summer orange #f99f00)

Exercise has emerged as a safe, effective, low-cost, non-pharmacological intervention for managing disability experienced by pwMS. Despite the evidence, it is the most under-prescribed and under-utilised disease-modifying therapy we have at our disposal.

Exercise promotes improvements in aerobic capacity, muscular strength, balance, walking performance, and gait kinematics, whilst it also reduces fatigue, depression and anxiety.

The meta-analysis below asks whether exercise training increases participation in everyday life, such as carrying out daily tasks and self-care, walking and movement, interpersonal relationships, and recreation and leisure. Are you surprised that the answer is YES?

EXERCISE INCREASES PARTICIPATION!

So for those of you who are letting ‘MS exile you from the everyday of life’ I would advise trying exercise to help you re-engage with the everyday.

Do any of you have any personal anecdotes that you can share with us about how exercise has changed your life?

Edwards et al. Exercise training improves participation in persons with multiple sclerosis: A systematic review and meta-analysis. Review J Sport Health Sci. 2021 Jul 26;S2095-2546(21)00089-2. doi: 10.1016/j.jshs.2021.07.007.

Objectives: While previous studies have examined the effects of exercise training on other International Classification of Functioning, Disability and Health (ICF) component levels in persons with multiple sclerosis (MS), the effects of exercise training on participation remains unclear. The objectives of this review were to: (1) systematically characterize the use of outcome measures that capture participation in exercise training studies; (2) quantify the effect of exercise training on participation in persons with MS.

Methods: A search of 6 electronic databases (CINAHL, Sport Discuss, EMBASE, MEDLINE, Cochrane Central, Scopus) was conducted to identify controlled and non-controlled trials involving exercise training and participation in persons with MS. Search strings were built from Medical Subject Headings (MeSH) and “CINAHL headings”. ICF linking rules were used to identify participation chapters and categories captured. Meta-analysis was used to quantify the effect of exercise training on participation in randomized controlled trials (RCTs) comparing exercise effects to no intervention/usual care.

Results: Forty-nine articles involving controlled and non-controlled exercise trials were included in the systematic review of outcome measures. Sixteen different outcome measures that captured all 9 participation chapters and 89 unique participation categories were identified. Across these 16 outcome measures, “mobility” was the most represented participation chapter, with 108 items. A subsample of 23 RCTs were included in the meta-analysis. An overall effect of 0.60 (standard error = 0.12, 95% confidence interval: 0.37-0.84, z = 4.9, p < 0.001) was calculated, indicating a moderate, positive effect of exercise training on participation.

Conclusion: The current review provides information that can be used to guide the selection of outcome measures that capture participation in studies of exercise training in persons with MS. Exercise training has a positive effect on outcomes that capture participation, providing further evidence for the role of exercise training in promoting and maintaining engagement in everyday life.

Keywords: ICF framework; exercise training; multiple sclerosis; participation.

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Mortality: what risk would you be prepared to take?

Barts-MS rose-tinted-odometer: ZERO-★’S (Black Tuesday – a tear for my beloved country #000000)

As you are aware by now I am a proponent of flipping the pyramid and using high-efficacy DMTs first-line including immune-reconstitution therapies (IRTs) such as alemtuzumab and AHSCT. I justify the latter two options based on the fact that given sufficient time the vast majority of pwMS will become disabled and the real cost of MS to people with MS cannot be underestimated; loss of employment, poor relationships, cognitive impairment, fatigue, depression, anxiety, etc. I think you get the gist; MS is a bad disease.

Alemtuzumab and HSCT are the two standout treatment options that offer pwMS the best chances of long-term remission and in some pwMS it may offer a cure. What impresses me about these two options is their impact on the end-organ, i.e. brain volume loss. After rebaselining at 12 months, pwMS treated with these two options lose brain volume on average at a rate that is within the normal range for age. The other DMTs don’t do this. The downside is that these two treatment options come with more risks. These two real-world studies below report 2 deaths out of 121 (2.5%) alemtuzumab-treated patients in Finland and 3 out of 120 HSCT-treated patients in London. Would you be willing to take these chances of dying to treat your MS with the potential for long term remission, possibly a cure and to protect your most precious end-organ the brain?

Rauma et al. Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients. J Neurol. 2021 Jul 13. doi: 10.1007/s00415-021-10664-w.

Background: Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice.

Objectives: To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients.

Methods: In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files.

Results: Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented.

Conclusions: SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.

Nicholas et al. Autologous Haematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: a Real-world Case Series. Neurology. 2021 Jul 12;10.1212/WNL.0000000000012449.

Objective: to examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting.

Methods: retrospective cohort study on PwMS treated with AHSCT at two centers in London, UK, consecutively between 2012 and 2019 who had ≥ 6 months of follow-up or died at any time. Primary outcomes were survival free of MS relapses, MRI new lesions and worsening of expanded disability status scale (EDSS). Adverse events rates were also examined.

Results: the cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS (RRMS). At baseline, the median expanded disability status scale (EDSS) was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6-85). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of subjects at 2 years and 85% at 4 years. EDSS progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. EBV reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplant-related deaths within 100 days (2.5%), all following fluid overload and cardiac or respiratory failure.

Conclusions: efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher.

Classification of evidence: this study is rated Class IV because of the uncontrolled, open-label design.

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Don’t walk and talk

Barts-MS rose-tinted-odometer: zero-★s (Blue Monday; Italian or Azzurri blue #0A36AF)

Have you noticed that you battle with multitasking? As MS progresses and damages the brain people with MS develop cognitive problems and have difficulty multitasking. This is because MS reduces your brain reserve and hence you have to concentrate on doing one task at a time. This is why pwMS have problems in the knowledge economy that requires cognitive multitasking and why so many pwMS have difficulty at work and often have to stop working relatively early in the course of their disease.

The study below shows this is not limited to cognition but physical activities as well. In the so-called walking-while-talking task they show how doing a mental task whilst walking causes your walking to deteriorate. I actually know of several patients who have had falls when taking on a mental task whilst walking. So please be careful if you are at risk of falls and have noticed problems with multitasking; don’t try to do two things at once, the consequences could be a fall and a fractured bone.

Have any of you noticed problems with multitasking affecting your walking ability and balance?

Henning et al. Validating the walking while talking test to measure motor, cognitive, and dual-task performance in ambulatory individuals with multiple sclerosis. Mult Scler Relat Disord. 2021 Jun 30;54:103123.

Introduction: Multiple Sclerosis (MS) is associated with demyelination of the central nervous system that negatively impacts both motor and cognitive function, resulting in difficulty performing simultaneous motor and cognitive tasks, or dual-tasks. Declines in dual-tasking have been linked with falls in MS; thus, dual-task assessment with the Walking While Talking Test (WWTT) is commonly utilized in the clinical setting. However, the validity and minimal detectable change (MDC) of the WWTT has not been established for persons with MS. The primary objective of the study was to establish the WWTT as a valid measure of dual-task function by examining concurrent validity with other motor, cognitive and dual-task measures, and to establish the MDC for both the simple and complex conditions of the WWTT.

Methods: In a single visit, 38 adults (34 female, mean (SD) age 49.8(±9.1), Patient Determined Disease Steps (PDDS) mean 3, range 1-6) completed the WWTT simple (walk while reciting the alphabet) and complex (walk while reciting every other letter of the alphabet) conditions as well as a battery of cognitive and motor tests. Spearman correlations were used to examine concurrent validity. The sample was divided into low and high disability groups to determine the impact of disability severity on relationships among WWTT and cognitive and motor function.

Results: Excellent concurrent validity (r ≥ 0.79; p < 0.001) was observed for the WWTT simple and complex with both motor (Timed Up-and-Go, Timed 25-Foot Walk, forward and backward walking velocity, Six-Spot Step Test) and dual-task measures (Timed Up-and-Go Cognitive). The WWTT-simple demonstrated moderate concurrent validity with measures of processing speed (Symbol Digit Modalities Test, p = 0.041) and was related to all motor and dual-task measures across disability levels. The WWTT complex was only related to complex motor tasks in the low disability group. Within the low disability group, WWTT was associated with processing speed (p = 0.045) and working memory (California Verbal Learning Test, p = 0.012). The MDC values were established for WWTT simple (6.9 s) and complex (8 s) conditions.

Discussion: The WWTT is a quick, easy-to-administer clinical measure that captures both motor and cognitive aspects of performance for persons with MS. Clinicians should consider adding the WWTT to the evaluation of persons with MS to examine dual-task performance.

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