Posted on Multiple Sclerosis

Stem cell transplants may delay disability longer than some Multiple Sclerosis medications

Tie One on for Multiple Sclerosis

In people with active secondary progressive multiple sclerosis (MS), hematopoietic stem cell transplants may delay disability longer than some other MS medications, according to a study published in the December 21, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study involved autologous hematopoietic stem cell transplants, which use healthy blood stem cells from a person’s own body to replace diseased cells.

While most people with MS are first diagnosed with relapsing-remitting MS, marked by symptom flare-ups followed by periods of remission, many people with relapsing-remitting MS eventually transition to secondary progressive MS, which does not have wide swings in symptoms but instead a slow, steady worsening of the disease.

“Hematopoietic stem cell transplants have been previously found to delay disability in people with relapsing-remitting MS, but less is known about whether such transplants could help delay disability during the more advanced stage of the disease,” said study author Matilde Inglese, MD, PhD, of the University of Genoa in Italy and a member of the American Academy of Neurology. “Our results are  encouraging, because while current treatments for secondary progressive MS have modest or small benefits, our study found stem cell transplants may not only delay disability longer than many other MS medications, they may also provide a slight improvement in symptoms.”

The retrospective study included 79 people with active secondary progressive MS who received stem cell transplants and 1,975 people from the Italian MS registry who were treated with MS drugs. All received treatment after being diagnosed with active secondary progressive MS. The two groups were matched for age, sex and level of disability. Drugs included beta-interferons, azathioprine, glatiramer acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate and alemtuzumab.

Participants’ level of disability was measured on the Expanded Disability Status Scale, a common method to quantify disability with scores ranging from 0, no symptoms, to 10 points, death due to MS. Participants were assessed at various time points over 10 years.

At the beginning of the study, participants had a median score of 6.5 for both those who received transplants and those receiving the medications. Scores of 6.0 are defined as needing to use a cane or brace intermittently or on one side to walk about 100 meters with or without resting. Scores of 6.5 are defined as needing to use a cane or brace constantly on both sides to walk about 20 meters without resting.

Five years into the study, researchers found 62% of the people who had stem cell transplants experienced no worsening of their MS disability compared to 46% of those who took medications.

Also, at five years, researchers found people who received stem cell transplants were more likely to see sustained improvements over time, with 19% experiencing less disability than at the start of the study, compared to just 4% of people taking medications.

Over 10 years, the disability score for people who had stem cell transplants decreased by an average of 0.01 points per year, signifying less disability, while the average score for people taking medications increased by 0.16 points per year, an increase in disability.

“Our study shows that hematopoietic stem cell transplants were associated with a slowing of disability progression and a higher likelihood of disability improvement compared to other therapies,” said Inglese. “While these results are encouraging, they are not applicable to patients with secondary progressive MS who do not have signs of inflammatory disease activity; more research is needed in larger groups of people to confirm our findings.”

A limitation of the study is that it was retrospective and observational, and does not prove cause and effect. It only suggests an association. The study also did not include people taking the MS drugs siponimod, cladribine, ocrelizumab, ofatumumab, or rituximab.

Posted on Diabetes, Diet

Understanding the “eating just one potato chip is impossible” gene

Mechanism by which CREB-Regulated Transcription Coactivator 1 (CRTC1) suppresses overeating


Osaka Metropolitan University scientists have revealed that the transcription cofactor gene CRTC1 mediates the obesity-suppressing effects of melanocortin-4 receptor (MC4R) by regulating appetite for fats and oils, high-fat diet metabolism, and blood sugar. CREDIT Shigenobu Matsumura, Osaka Metropolitan University

High-calorie foods—high in fat, oil, and sugar—can taste good but often cause overeating, leading to obesity and major health problems. But what stimulates the brain to cause overeating?

Recently, it has become clear that a gene called CREB-Regulated Transcription Coactivator 1 (CRTC1) is associated with obesity in humans. When CRTC1 is deleted in mice, they become obese, indicating that functioning CRTC1 suppresses obesity. However, since CRTC1 is expressed in all neurons in the brain, the specific neurons responsible for suppressing obesity and the mechanism present in those neurons remained unknown.

To elucidate the mechanism by which CRTC1 suppresses obesity, a research group led by Associate Professor Shigenobu Matsumura from the Graduate School of Human Life and Ecology at Osaka Metropolitan University focused on neurons expressing the melanocortin-4 receptor (MC4R). They hypothesized that CRTC1 expression in MC4R-expressing neurons suppressed obesity because mutations in the MC4R gene are known to cause obesity. Consequently, they created a strain of mice that expresses CRTC1 normally except in MC4R-expressing neurons where it is blocked to examine the effect that losing CRTC1 in those neurons had on obesity and diabetes.

When fed a standard diet, the mice without CRTC1 in MC4R-expressing neurons showed no changes in body weight compared to control mice. However, when the CRTC1-deficient mice were raised on a high-fat diet, they overate, then became significantly more obese than the control mice and developed diabetes.

“This study has revealed the role that the CRTC1 gene plays in the brain, and part of the mechanism that stops us from overeating high-calorie, fatty, and sugary foods,” said Professor Matsumura. “We hope this will lead to a better understanding of what causes people to overeat.”

Posted on Multiple Sclerosis

Myelin determines energy metabolism in inhibitory brain cells

Researchers at the Netherlands Institute for Neuroscience have discovered that the energy management of inhibitory brain cells is different compared to excitatory cells in our brain. Why is that the case and what is the link with multiple sclerosis?

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Brain cells are connected to each other by axons, the parts of the neuron that transmit electrical signals. To do this efficiently, axons are wrapped in myelin, a lipid-rich material which increases the speed at which electrical pulses are conducted. The importance of myelin becomes apparent in diseases such as multiple sclerosis (MS), where myelin is broken down, which has detrimental effects on brain function. As a result of myelin loss, the conduction of electrical signals is disrupted, which also means that the energy costs of this process become much higher.

Myelin behaves differently depending on the cell type. Our brain consists of both excitatory and inhibitory brain cells. We need these inhibitors, known as interneurons, to structure the symphony of the many electrical pulses in our brain. When stimulating brain cells are randomly active with no brakes to direct this activity, communication between brain cells becomes less precise. Interneurons are therefore of great importance for efficient functioning of our brain.

The team around researcher Koen Kole and his supervisor Maarten Kole looked at a special type of interneuron: the Parvalbumin or PV cell. Although PV cells occupy only a small percentage of the cells in the cerebral cortex, they are very good at controlling surrounding networks of brain cells. This is mainly because of their extensive axons with many branches. They also have a high level of electrical activity. This costs a lot of energy, but it does ensure that PV cells can effectively inhibit surrounding cells. Remarkably, PV cells are wrapped with myelin only in the first few branches of their axon, leaving large parts of the axon uncovered. So what exactly does myelin do in these cells?

Myelin does appear to be important in PV cells. Previous studies on tissue from MS patients showed that PV cells die when myelin is lost. Apart from conduction, myelin also plays an important role in nourishing the cell. Nutrients from the myelin can be absorbed by mitochondria, the energy factories of the cell. Since PV cells use a lot of energy, it has been thought that myelin in these cells might play an important role in supporting the energy production of mitochondria.

Opposite effect from other cell types

The new study shows that this is indeed the case, in contrast to other cell types. In excitatory brain cells, mitochondria were evenly distributed along the axon, but in PV cells, the team found that axons with myelin contained more mitochondria. And when the myelin is reduced in an experimental setting, PV cells showed a decrease in the amount of mitochondria whereas in excitatory cells mitochondria become more abundant. And that’s new. In PV cells, mitochondria behave in an opposite way from what was previously known in the literature for other types of cells. But why exactly does this happen in these cells?

Researcher Koen Kole: ‘We suspect that it has to do with the fact that PV cells have an incredibly high energy demand due to their high level of activity. In addition, their axons are very thin compared to those of other cell types, which could further increase their energy consumption. PV cells may therefore be more dependent on external nutrients from the myelin. A next important step would be to better understand how myelin influences the energy usage in the axons of PV cells. Abnormalities in PV cells and mitochondria can be found in many other neurological disorders besides MS. It is therefore of high importance to gain more insight into the energy management in this cell type.’

Posted on Autism, Diabetes

Does diabetes during pregnancy increase the risk of neurodevelopmental conditions (such as autism) in children?

Children talking
Children talking

New research published in Developmental Medicine & Child Neurology has revealed a link between maternal diabetes during pregnancy and a range of neurodevelopmental conditions in children—including autism, attention-deficit/hyperactivity disorder (ADHD), developmental delay, intellectual disability, cerebral palsy, and epilepsy.

The retrospective study included 877,233 children born between 2004 and 2008 in Taiwan whose mothers had type 1, type 2, or gestational diabetes during pregnancy. The effect of type 1 diabetes on neurodevelopmental disorders was the largest, followed by type 2 diabetes, and then gestational diabetes.

Type 1 diabetes was associated with an increased risk of developmental delay, intellectual disability, and epilepsy in children. Type 2 diabetes was associated with an increased risk of autism spectrum disorder, ADHD, developmental delay, intellectual disability, cerebral palsy, and epilepsy. Gestational diabetes was associated with an increased risk of autism spectrum disorder, ADHD, and developmental delay.

“Mechanistic studies are needed to explore how maternal conditions, such as diabetes, may shape brain development in the womb,” said corresponding author Pao-Lin Kuo, MD, of National Cheng Kung University Hospital. 

Posted on Autism

Suicidal teens and other autistic kids in mental health crisis languish in ERs, study finds – how would you solve this?

Autism and Teens in Hospital
Autism and Teens in Hospital


Every day across America, hundreds of children and teens with depression, anxiety, autism and other conditions end up in their local hospital’s emergency department because of a mental or behavioral health crisis.

And 12 hours later, 1 in 5 of them will still be in the ED, a study finds.

Another 12 hours after that – a full day after they arrived – 1 in 13 of them will still be in the ED. More than 60% of these patients are suicidal or have engaged in self-harm.

Meanwhile, virtually all the children who went to the same hospital for non-mental health emergencies have already received treatment and gone home, or been admitted to the hospital, within 12 hours, the study shows.

Visits of both kinds dropped dramatically in spring 2020, and even a year and a half later, non-mental health emergency visits by kids were still below pre-pandemic levels. But mental health emergency visits climbed steadily. By early 2021 they had exceeded their pre-pandemic levels and stayed there, with seasonal variation.

The study, published in the Journal of the American College of Emergency Physicians Open by a team led by an emergency physician from the University of Michigan and VA Ann Arbor Healthcare System, adds more evidence of the strain faced by the pediatric mental health system. It builds on previously reported data from large teaching hospitals and children’s hospitals.

“Insufficient access to mental health care stands out among the factors that contribute to prolonged stays in the nation’s emergency departments,” said first author Alex Janke, M.D., M.H.S., a National Clinician Scholar at VAAHS and the U-M Institute for Healthcare Policy and Innovation. “There are too few options outside of emergency care for patients in many communities.”

About 1 in 8 children who go to a community hospital for a mental health emergency end up getting admitted for at least one night or transferred to another hospital, the study finds. That number rose beyond pre-pandemic numbers by early 2021 and has stayed high ever since. Meanwhile, children’s admissions and transfers for other types of emergencies have stayed flat.

Because the hospitals in the study are not part of major academic systems, they likely do not always have child psychiatrists or other specialists in-house to work with emergency medicine teams in assessing and creating treatment plans for children in mental health crisis.

Janke and his colleagues from Yale University, the American College of Emergency Physicians and Columbia University used data from the Clinical Emergency Data Registry, with data from 107 community hospitals from January 2020 to December 2021, plus data from 2019 from 33 of those hospitals.

The majority of emergency department visits by children and teens in the United States happen in such hospitals, Janke notes. More resources that could help families get care in the local community or via telehealth could reduce the need to seek emergency care for their child, he says. Also needed are more resources to support local emergency medicine teams who find themselves caring for a child or teen in mental health crisis.

“While others are studying the epidemiology of mental health concerns among American’s youth at this point in the pandemic, our study focuses on whether the mental health system is ready for what’s coming in the door,” he said. “And the length of emergency department stays that we’re seeing here shows that it is not.”

The data source does not contain information about individual characteristics of the patients seeking care, such as what kinds of mental health care they’ve received, their demographic information, or what caused their families to seek emergency mental health care.

Janke and colleagues are working on further research on this topic. But the study does show that hospitals in the northeastern part of the country were most likely to have longer ED stays than other regions, especially the south and west.

The study does not measure “boarding” times, which is the time between an emergency care clinician’s decision to admit a patient to the time that patient actually leaves the ED for a bed in that hospital or another facility. But in a paper published earlier this year, Janke and colleagues showed that by the end of 2021, median boarding times for adult emergency patients were approaching the nationally recommended level of 3.4 hours.

If you, your child or someone you know is having a mental health crisis or considering suicide, contact the national 988 Suicide and Crisis Lifeline by calling or texting 988, or visiting 988lifeline.org for crisis chat services or for more information.