Posted on Multiple Sclerosis

MS experts call for increased focus on progressive MS rehabilitation research

Dr. DeLuca, an expert in cognitive MS research, is senior vice president of Research and Training at Kessler Foundation. CREDIT Kessler Foundation

An international team of multiple sclerosis (MS) experts has identified four under-researched areas that are critical to advancing symptom management for progressive MS, recommending interdisciplinary collaboration among scientists, clinicians, industry leaders, and those with progressive MS. Their call to action was published in Multiple Sclerosis Journal on March 15, 2021, in the article “Prioritizing progressive MS rehabilitation research: A call from the International Progressive MS Alliance” (doi: 10.1177/1352458521999970). The Alliance was represented by authors from Canada, the United States, the UK, Australia, Denmark, Belgium, Germany, and Switzerland.

Recent advances in MS research have resulted in a variety of disease-modifying therapies that can significantly improve quality of life for people with certain phenotypes of the disease. For example, those with relapsing-remitting MS have access to more than 20 therapies. However, these phenotypes represent only some in the MS community.

A major barrier to the development of rehabilitation therapies for progressive MS is the fact that the vast majority of studies conducted to explore rehabilitative therapies involve people with relapsing-remitting MS, not progressive MS. In addition, trials are often designed based on strategies used for pharmaceutical trials, which are not necessarily conducive to clinical rehabilitation trials. Unfortunately, this lack of clinical data to inform therapies for progressive MS leaves this population with few options to manage potentially debilitating symptoms that can lead to challenges such as loss of a job, personal and family stress, and financial strain.

In this article, experts from research, medicine, and industry highlight four major symptoms affecting people with progressive MS that should be the focus of new research: fatigue, mobility and upper extremity impairment, pain, and cognitive impairment. They contend that rehabilitative therapies show great promise for managing these symptoms and for improving physical and cognitive function as well as quality of life, and that directing research efforts toward rehabilitation is critical to developing effective therapies.

“There is a strong need to study the effect of early preventive interventions and to evaluate management of existing symptoms,” says co-author John DeLuca, PhD, Senior Vice President for Research and Training at Kessler Foundation. “Effective symptom management and rehabilitation remain far behind in progressive MS. We have little empirical rehabilitation data, and our understanding of mechanisms underlying symptoms and treatment responses is incomplete.” Dr. DeLuca emphasizes, “We have ample evidence from research in other clinical areas that rehabilitation can improve quality of life and find support from diverse payers and stakeholders. Our aim is to bring attention to the pressing need to develop rehabilitation treatment interventions for the progressive MS community.”

Posted on Multiple Sclerosis

Exoskeleton therapy improves mobility, cognition and brain connectivity in people with Multiple Sclerosis

A pilot study led by Kessler Foundation researchers provided proof of concept for robotic-exoskeleton assisted exercise rehabilitation (REAER) in people with substantial MS-related neurological disability

A research participant in the MS pilot study does exercise training in the Ekso NR at Kessler Foundation. CREDIT Kessler Foundation/Jody Banks

 A team of multiple sclerosis (MS) experts at Kessler Foundation led the first pilot randomized controlled trial of robotic-exoskeleton assisted exercise rehabilitation (REAER) effects on mobility, cognition, and brain connectivity in people with substantial MS-related disability. Their results showed that REAER is likely an effective intervention, and is a promising therapy for improving the lives of those with MS.

The article, “A pilot randomized controlled trial of robotic exoskeleton-assisted exercise rehabilitation in multiple sclerosis,” (doi: 10.1016/j.msard.2021.102936) was published on April 4, 2021, by Multiple Sclerosis and Related Disorders. It is available open access at https://www.msard-journal.com/article/S2211-0348(21)00203-0/fulltext.

The authors, are Ghaith J. Androwis, PhD, Brian M. Sandroff, PhD, Peter Niewrzol, MA, Glenn R. Wylie, DPhil, Guang Yue, PhD, and John DeLuca, PhD, of Kessler Foundation, and Farris Fakhoury, DPT, of Kessler Institute for Rehabilitation.

It is common for people with MS to experience impairments in both mobility and cognition, and few therapies exist to manage the range of debilitating symptoms. This lack of treatment options is a major problem for people with MS, especially those with substantial MS-related neurological disability.

Previous research shows that exercise rehabilitation, such as walking, is an effective approach to symptom management, with some research suggesting that even a single exercise rehabilitation intervention can improve both mobility and cognition.

Yet there is a lack of efficacy of exercise rehabilitation on mobility and cognitive outcomes in people with MS who have substantial disability. Adaptive exercise rehabilitation approaches such as body-weight supported treadmill training and robot-assisted gait training have not demonstrated convincing results. Moreover, adaptive interventions lack key interactions between patients and therapists that may improve efficacy.

In this pilot study of 10 participants with significant MS-related neurological disability, researchers explored the use of robotic exoskeletons to manage symptoms. Rehabilitation exercise using robotic exoskeletons is a relatively new approach that enables participants to walk over-ground in a progressive regimen that involves close engagement with a therapist. The Foundation has dedicated a Ekso NR to MS studies to facilitate further research in this area.

As compared to conventional gait training, REAER allows participants to walk at volumes needed to realize functional adaptations–via vigorous neurophysiological demands–that lead to improved cognition and mobility. Effects on brain activity patterns were studied using the functional MRI capabilities of the Rocco Ortenzio Neuroimaging Center at Kessler Foundation.

Investigators compared participants’ improvement after four weeks of REAER vs four weeks of conventional gait training, looking at functional mobility, walking endurance, cognitive processing speed, and brain connectivity.

The results were positive: Relative to conventional gait training, four weeks of REAER was associated with large improvements in functional mobility (ηp2=.38), cognitive processing speed (ηp2=.53), and brain connectivity outcomes, most significantly between the thalamus and ventromedial prefrontal cortex (ηp2=.72). “Four weeks is relatively short for an exercise training study,” noted Dr. Sandroff, senior research scientist at Kessler Foundation and director of the Exercise Neurorehabilitation Research Laboratory. “Seeing improvements within this timeframe shows the potential for exercise to change how we treat MS. Exercise is really powerful behavior that involves many brain regions and networks that can improve over time and result in improved function.”

“This is particularly exciting because therapy using robotic exoskeletons shows such promise for improving the lives of people with co-occurring mobility and cognitive disability, a cohort that likely has the greatest potential to benefit from this new technology,” said Dr. Androwis, lead author and research scientist in the Center for Mobility and Rehabilitation Engineering Research at Kessler Foundation. “We’re eager to design a larger trial to further study these effects. Based on our initial results, we’re optimistic that this approach may be superior to the current standard of care.”


Posted on Sleep disorders

Is there a certain sleep cycle we should all adhere to?

Is there a certain sleep cycle we should all adhere to?
Is there a certain sleep cycle we should all adhere to?

“Absolutely, our own one and we shouldn’t deviate from it!”

We humans all adhere to our Circadian rhythms or the 24-hour sleep/wake cycle. Within that 24-hour period we are awake, active, sleep then awake again. However, the actual timing of this differs from person to person because we are governed by our genetics on this one.

It’s called our ‘Chronotype’. There are two main types: Morning Larks or Night Owls. Larks naturally go to bed and get up early and Owls are the opposite. Most people fall into one of these two categories. This harps back to when we were cave-dwelling hunter/gatherers. To ensure we would be successful with our endeavours (and to increase our safety) there were effectively two shifts, morning, and evening.

Simple Sleeping Habits:

  1. “Don’t force yourself to stay up all night if you’re a Lark and don’t take yourself off to bed at nine o’clock in the evening if you’re an Owl.”
    Accept your genetic propensity to sleep and stick to it, you’ll notice a decrease in stress and an increase in vitality.
  2. “Another habit to acquire is to ditch the tech an hour before bed and make the sleep environment as dark as possible.”
    This gives the brain a very clear signal to start producing the sleep hormone melatonin.
    In the morning, get as much light into the eyes as possible, this stops melatonin production.
  3. “Another recommendation is to stay hydrated but avoid sugary drinks.”
     This is all simple and obvious, but the best advice usually is.

How does sleep affect us?

“A thing to remember about sleep is that it is a very complex series of 90-minute cycles which are broken down into stages. Each stage performs a different task and one of these is to repair damaged cells and flush out toxins. This can only happen when we allow a cycle to complete and are hydrated enough for efficient flushing. When we sleep well, we feel well. I don’t know about you but when I’ve had a great night’s sleep my stress levels are low, my productivity is high, and I feel like I can cope with life so much easier.”

Posted on ADHD, Autism

Prenatal exposure to paracetamol associated with ADHD and autism in childhood

Prenatal exposure to paracetamol associated with ADHD and autism symptoms in childhood
Prenatal exposure to paracetamol associated with ADHD and autism symptoms in childhood

An epidemiological study of more than 70,000 children in six European cohorts has linked symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum conditions (ASC) to the mothers’ use of paracetamol (acetaminophen) during pregnancy. The study, published in the European Journal of Epidemiology, was led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the “la Caixa” Foundation.

In total, the researchers analysed 73,881 children for whom data were available on prenatal or postnatal exposure to paracetamol, at least one symptom of ASC or ADHD, and main covariates. Depending on the cohort, 14% to 56% of the mothers reported taking paracetamol while pregnant.

The study found that children exposed to paracetamol before birth were 19% more likely to develop ASC symptoms and 21% more likely to develop ADHD symptoms than children who were not exposed.

“Our findings are consistent with previous research,” explained ISGlobal researcher Sílvia Alemany, lead author of the study. “We also found that prenatal exposure to paracetamol affects boys and girls in a similar way, as we observed practically no differences.”

“Our results address some of the weaknesses of previous meta-analyses,” commented Jordi Sunyer, researcher at ISGlobal and last author of the study. “Considering all the evidence on the use of paracetamol and neurological development, we agree with previous recommendations indicating that while paracetamol should not be suppressed in pregnant women or children, it should be used only when necessary.”

At some point during pregnancy, an estimated 46%-56% of pregnant women in developed countries use paracetamol, which is considered the safest analgesic/antipyretic for pregnant women and children. However, mounting evidence has linked prenatal paracetamol exposure to poorer cognitive performance, more behavioural problems, and ASC and ADHD symptoms.

Those previous studies have been criticised for their heterogeneity. In the new study, therefore, “an effort was made to harmonise the assessment of ADHD and ASC symptoms and the definition of paracetamol exposure,” explained Alemany. “The sample is large,” she added, “and it includes cohorts from multiple European countries: the United Kingdom, Denmark, the Netherlands, Italy, Greece and Spain. We also used the same criteria for all of the cohorts, thereby reducing the heterogeneity of criteria that has hampered previous studies.”

The study also analysed postnatal exposure to paracetamol and found no association between paracetamol use during childhood and ASC symptoms. Nevertheless, the research team concluded that further studies are needed, given the heterogeneity of postnatal paracetamol exposure among the various cohorts, which ranged from 6% to 92.8%.

The six cohorts included the study were as follows:

Posted on Autism

Autism – National database reveals a cumulative incidence of 2.75%

Autism Spectrum Disorder - National database reveals a cumulative incidence of 2.75%
Autism Spectrum Disorder – National database reveals a cumulative incidence of 2.75%


Analysis using a national medical database revealed that the cumulative incidence of autism in children born in 2009-2014 was 2.75% by the age of five. A research group led by Associate Professor Daimei Sasayama and Professor Hideo Honda of the Department of Child and Adolescent Development Psychiatry, Shinshu University School of Medicine, used a national medical database to analyze autism spectrum disorders in Japan. It was reported that the cumulative incidence showed an increasing trend for each year of birth, and that there were regional differences.

This cumulative incidence of autism is the highest in the world based on medical diagnosis, suggesting high diagnostic sensitivity in Japan. The proportion of people diagnosed with autism has increased globally over the last 20 years, with a 2014 US survey reporting a prevalence of 1.68% in 8-year-olds. In addition, a regional cohort study of children’s mental development and psychiatry at Shinshu University School of Medicine reported that 3.1% of children had been diagnosed with autism spectrum disorders by school age. Improving screening accuracy is one of the main reasons why more and more people are being diagnosed with autism spectrum disorders. In order to investigate the actual condition of diagnosis of autism spectrum disorder in Japan, the group investigated the cumulative incidence of autism spectrum disorder nationwide and the cumulative incidence by prefecture using National Database (NDB), which aggregates medical data from all over the country.

For children born in 2009-2016 and diagnosed with autism spectrum disorder in 2009-2019, information on gender, year and age at the time of diagnosis, and the prefecture where the diagnosis was made were extracted from NDB. Cumulative incidence was calculated by dividing the number of diagnoses by the number of births each year.

Of the children born in 2009-2016, 313,353 (236,386 boys, 76,967 girls) were diagnosed with autism spectrum disorder in 2009-2019. The lifetime cumulative incidence of autism at age 5 in children born between 2009 and 2014 was 2.75%. The cumulative incidence tended to increase with each year of birth. By prefecture, the cumulative lifetime incidence of autism at age 5 ranged from 0.9-7.9% (median 2.4%).

This study published in the journal JAMA Network Open reported that the cumulative incidence of autism spectrum disorders in Japan is high worldwide. It is thought that the nationwide increasing trend is influenced by the recent increase in awareness of autism . On the other hand, since there are large regional differences in the incidence rate, it is possible that factors such as differences in access to medical care and support also affect the incidence rate. The results of this study show that there is an increasing need to build a support system for autism . Accurately capturing changes in the frequency of autism spectrum disorders is important both for the realization of an effective support system and for studying the risk factors and etiology of autism spectrum disorders. The research group will continue to investigate trends in the incidence of autism spectrum disorders in Japan and around the world.