Cigarette smoking is a well-recognised risk factor for stroke and measures to reduce the prevalence of cigarette smoking have been implemented in many countries. The use of electronic cigarettes (vaping) has been advocated as a strategy to help smokers to quit.  Carla Silva (Mersey and West Lancashire Teaching Hospitals NHS Trust, United Kingdom) reported the case of a young male, never-smoker, heavy vaper, who sustained injury to the spinal cord as a result of an infarct.¹

A 21-year-old male brick-layer experienced a sharp pain in the back of his neck whilst at work. He initially tried to ignore the pain but soon noticed pins and needles to his body and muscle weakness to his arms and legs. He stopped what he was doing and tried to sit down but became clammy and sweaty and was struggling for air. He was taken by ambulance to the local Emergency Department where it was noted that he needed ventilatory support to maintain adequate ventilation.

He had no known comorbidities. He had never smoked cigarettes but smoked e-cigarettes “all the time”, estimating an equivalent of 100 cigarettes per day since the age of 11.

MRI of the whole spine showed a spinal cord infarct at C2-C5 level, with hyper-acute onset. No other injuries were noted.  Other investigations were unremarkable.

The patient was referred to a rehabilitation centre for a comprehensive rehabilitation programme. At admission, peripheral neurological examination revealed incomplete tetraplegia AIS D at C3 level, as per the International Standards for Neurological Classification of Spinal Cord Injury, in central cord syndrome type of injury, with no hand function.

Silva concluded that:

• Spinal cord infarct remains an uncommon cause of spinal cord injury, compared to traumatic injury and other non-traumatic causes (e.g. infection, spinal tumours).
• Spinal cord infarct is a rare ischaemic occurrence, representing only a fraction of all ischaemic strokes (1%).
• The possible impacts of e-cigarette usage, including long-term toxicological and immunological effects, are not yet fully understood.
• Acute spinal cord ischaemia is life-changing for the individual and expected clinical outcomes are still unclear.

Reference

1. Silva C. Case report: spinal cord infarct secondary to vaping? (Poster) EAHP Congress 2025

Notwithstanding wide regional variations, platinum based drugs, taxanes, and lung cancer seem to be associated with the highest rates of persistent painful neuropathy, lasting at least 3 months, the findings suggest, prompting the researchers to call for tailored approaches to pain relief.

The drugs used to treat cancer damage healthy cells and tissues, including the nervous system. The effects can manifest in movement disturbances, such as loss of balance or coordination, and sensory disturbances, such as loss of sensation; numbness, tingling, “pins and needles”; or a burning sensation on the skin.

Several factors influence the frequency and severity of chronic peripheral neuropathic pain, including type and dose of chemotherapy, pre-existing neuropathy, and the use of other drugs that can damage the nervous system, explain the researchers.

The condition is thought to be caused by direct peripheral nerve cell damage which disrupts or rewires normal nerve signalling pathways, resulting in persistent pain, they add.

Prompted by the growing number of cancer survivors and increasingly aggressive treatment of the disease, the researchers wanted to gauge the global prevalence of chronic painful peripheral neuropathy linked to chemotherapy.

They scoured research databases for relevant studies published between 2000 and 2024, focusing on potentially influential sociodemographic, clinical, and methodological (study design, funding source, for example) factors.

In all, they pooled the results of 77 eligible studies, involving 10,962 participants from 28 countries, all of whom had peripheral neuropathy that was associated with cancer drug treatment. In 4545 of these participants, this was painful and persistent, lasting for at least 3 months.

The highest number of studies were carried out in the US (13) and Japan (10), and almost half were prospective observational studies.

The cancers that featured most often were those of the bowel (25; 33%) and breast (17; 22%), while the largest proportion of studies focused on patients treated with either platinum based agents (13;17%), or taxanes (11; just over 14%), or both (6 ;8%), or the FOLFOX combination of folinic acid plus 5-fluorouracil plus oxalplatin (5; 6.5%).

Pooled data analysis of the study results showed that the overall prevalence of persistent painful peripheral neuropathy was just over 41%.

When stratified further, the analysis indicated that the highest prevalence was among patients treated with platinum based agents (40.5%) and taxanes (just over 38%). Prevalence was lowest among those treated with the FOLFOX combination (16.5%).

Prevalence was also highest among those with primary lung cancer (just over 62%), possibly because of the complexities of treatment for this disease, suggest the researchers. Prevalence was lowest among those with primary ovarian cancer (31.5%) and lymphoma (36%).

When stratified by continent, studies of patients in Asia reported the highest prevalence of persistent painful neuropathy (46.5%), while studies of patients in Europe reported the lowest (36%). Prevalence rates were similar in both men and women.

The researchers emphasise that the design and methodology of the included studies differed substantially. And the overall certainty of evidence was considered to be low.

But they write: “Understanding the prevalence and predictors of chronic painful [chemotherapy induced peripheral neuropathy] is critical for promoting early diagnosis and developing personalized treatment strategies.

“Our findings emphasize that chronic painful [chemotherapy induced peripheral neuropathy] represents a substantial global health challenge, affecting more than 40% of those diagnosed with [it].”

And they conclude: “The wide variability in prevalence rates across different countries, continents, chemotherapy regimens, and primary cancer history underscores the need for tailored strategies to address this debilitating condition.

“Future studies should focus on elucidating the mechanisms underlying these disparities and developing interventions that can reduce the burden of chronic painful [chemotherapy induced peripheral neuropathy] globally.”

Spinal cord injury is a life-changing condition that creates a need for hands-on help from others for important daily tasks. However, obtaining reliable, high-quality personal care assistance services is often challenging due to the high turnover rates among paid caregivers and insufficient knowledge among home health care workers about the unique needs of individuals living with spinal cord injury.

In response to these challenges, the web-based course, “Understanding Spinal Cord Injury,” was developed as a basic resource to help prepare PCAs for their integral role in the daily lives of people with spinal cord injury. The course’s core modules describe the types of spinal cord injury, common physical needs, personal and social challenges, and potential secondary complications, as well as common misunderstandings about the condition. Four modules address special topics, including building positive assistant-client relationships, managing blood pressure, understanding assistive technology and medical equipment, and transferring clients safely to and from their wheelchairs.

“For people with spinal cord injuries, routine personal care assistance is vital to preventing medical complications and facilitating their involvement at home, work, and school,” said Cheryl Vines, Director of Research and Education at PVA. “However, obtaining reliable, high-quality services is often challenging due to the high turnover rates among paid caregivers and insufficient knowledge among home health care workers about the unique needs of individuals living with spinal cord injuries.” Collaboration was fundamental to the course’s development, according to Dr. Zanca, the project’s director. Guided by a steering committee of people with real-world experience with spinal cord injury—including PCAs, home health care agency leaders, trainers, family members, and rehabilitation clinicians—the modules were developed by Kessler Foundation in collaboration with Shepherd Center. The National Institute on Disability, Independent Living, and Rehabilitation Research NIDILRR) and the Paralyzed Veterans of America (PVA) Education Foundation provided funding.

“Focus groups and interviews were conducted with people with spinal cord injury, family caregivers, clinicians, and experienced PCAs,” Dr. Zanca explained, “to ensure that the modules reflect the priorities of individuals with spinal cord injury as well as the educational needs of assistants.”

Recognizing its focus on client-centered care for spinal cord injury, the North American Spinal Cord Injury Consortium (NASCIC) has endorsed the new course. “We at NASCIC firmly believe in the principle of people with lived experience of spinal cord injury working in partnership with their caregivers, clinicians, and researchers,” said Barry Munro, treasurer of NASCIC. “As a person with tetraplegia who is dependent on attendant care, I feel all caregivers for people with spinal cord injury should take this course,” advised Munro. “I only wish such a valuable resource had been available years ago.”

The course was pilot tested by personal care assistants without prior experience with spinal cord injury care. “Their feedback was positive,” Dr. Zanca  said, “indicating that they gained practical information by completing the course and felt prepared to work effectively with clients with spinal cord injury.”

“Understanding Spinal Cord Injury: A Course for Personal Assistants,” is a significant step towards ensuring the quality of personal care assistance services provided to individuals living with spinal cord injury,” Dr. Zanca emphasized. “Now we are working with our partners to disseminate this resource to the wider community of individuals, families, and professionals who are invested in improving quality of life after spinal cord injury.”

Dr. Zanca’s presentation will also be offered at the annual meetings of the Academy of Spinal Cord Injury Professionals in San Diego, CA (Sept. 3-6), and the American Congress of Rehabilitation Medicine in Atlanta, GA (Oct. 28-Nov 1).

This initiative was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR Grant #90IF0115) and the Paralyzed Veterans of America Education Foundation (Grant #862).

IMAGE: A WOMAN IS SITTING IN A WHEELCHAIR NEXT TO HER MALE PERSONAL CARE ASSISTANT AT AN OUTSIDE TABLE SURROUNDED BY GREENERY. BOTH ARE SMILING BROADLY. view more 

CREDIT: KESSLER FOUNDATION

The research, published in British Journal of Clinical Pharmacology, found that the KCL-286 drug – which works by activating retinoic acid receptor beta (RARb) in the spine to promote recovery – was well tolerated by participants in a Phase 1 clinical trial, with no severe side effects. Researchers are now seeking funding for a Phase 2a trial studying the safety and tolerability of the drug in those with SCI.

Global prevalence of SCI is estimated to be between 0.7 and 1.2 million cases per year, with falls and road accidents being the major causes. Despite incurring a cost of $4 billion per year in direct healthcare and indirect costs (i.e. inability to work and social care) in the US alone, there are no licensed drugs that can tackle the intrinsic failure of the adult central nervous system to regenerate, and thus remains a largely unmet clinical need.

Previous research by various groups has shown that nerve growth can be stimulated by activating the RARb2 receptor, but no drug suitable for humans has been developed. KCL-286, an RARb2 agonist¹, was developed by Professor Corcoran and team and used in a first in man study to test its safety in humans.

109 healthy males were divided into one of two trial groups; single ascending dose (SAD) adaptive design with a food interaction (FI) arm, and multiple ascending dose (MAD) arm. Participants in each arm were further divided into different dose treatments.

SAD studies are designed to establish the safe dosage range of a medicine by providing participants with small doses before gradually increasing the dose provided. Researchers look for any side effects, and measure how the medicine is processed within the body. MAD studies explore how the body interacts with repeated administration of the drug, and investigate the potential for a drug to accumulate within the body.

Researchers found that participants were able to safely take 100mg doses of KCL-286, with no severe adverse events.

Professor Jonathan Corcoran, Professor of Neuroscience and Director of the Neuroscience Drug Discovery Unit, at King’s IoPPN and the study’s senior author said, “This represents an important first step in demonstrating the viability of KCL-286 in treating spinal cord injuries. This first-in-human study has shown that a 100mg dose delivered via a pill can be safely taken by humans. Furthermore, we have also shown evidence that it engages with the correct receptor.

“Our focus can hopefully now turn to researching the effects of this intervention in people with spinal cord injuries.”

Dr. Bia Goncalves, a senior scientist and project manager of the study, and the study’s first author from King’s IoPPN said, “Spinal Cord Injuries are a life changing condition that can have a huge impact on a person’s ability to carry out the most basic of tasks, and the knock-on effects on their physical and mental health are significant.

“The outcomes of this study demonstrate the potential for therapeutic interventions for SCI, and I am hopeful for what our future research will find.”

This work was possible thanks to funding from the Medical Research Council.

“While two injectable therapies known as platform injectables, were once the mainstay of multiple sclerosis treatment, our study showed oral therapies became the predominate treatment for multiple sclerosis by 2020,” said Mackenzie Henderson, a postdoctoral researcher at the Rutgers Institute for Health, Health Care Policy and Aging Research (IFH) and the lead author of the study. “Our investigation offers an important step in understanding the evolving treatment landscape for MS among U.S. adults and children.”

The study, published in JAMA Neurology, examined a large and diverse sample of commercially insured adults and children in the United States to evaluate trends in uptake of therapies between 2001 and 2020 for patients with MS, a chronic and progressive neurological disorder and the leading cause of nontraumatic disability among young and middle-aged adults.

In 2000, there were two medications approved for MS treatment in the U.S., but over the past 20 years, more than 10 new medications have been approved, according to researchers.

Research on how these approvals have changed clinical practice has been limited. The Rutgers study shows injectable therapies accounted for nearly 100 percent of medications for MS patients in 2001, but by 2020 that decreased to about 25 percent, with oral therapies rising sharply after their introduction in 2010.

Using commercial claims data from more than 100,000 patients with MS between 2001 and 2020, researchers analyzed injectable, infusion and oral treatment trends. They found that oral medications increased sharply in popularity to become the preferable treatment for MS patients over infusion and injectable treatments. Infusion therapies remained low in uptake, accounting for about 8 percent of therapy initiations in 2020, and platform injectable therapy use declined almost 74 percent throughout the study period, according to researchers.

“Despite the availability and efficacy of infusion therapies for multiple sclerosis, we found that their utilization remained relatively low throughout the study period,” said Chintan Dave, a faculty member at the Center for Pharmacoepidemiology and Treatment Science (PETS) at IFH, an assistant professor with Rutgers Ernest Mario School of Pharmacy and a senior author of the study. “This may be due to several factors contributing to this treatment decision by patients and clinicians, including the preference for more convenient oral therapies, the relatively recent introduction of infusion options, and considerations of safety and cost.”

Researchers said this investigation offers a crucial step in understanding the evolving treatment landscape for MS patients and future research should evaluate the impact of new therapies as they emerge.

Coauthors of the study include Daniel Horton of PETS, Rutgers Robert Wood Johnson Medical School and the Rutgers School of Public Health; Greta Bushnell of PETS and the Rutgers School of Public Health; and Vikram Bhise and Gian Pal of Rutgers Robert Wood Johnson Medical School.

Henderson was the first graduate of Rutgers School of Public Health’s Master of Science in Epidemiology program with a concentration on pharmacoepidemiology.

Depressive symptoms cause a significant disease burden worldwide. The therapeutic efficacy of current antidepressants is often insufficient, which is why further ways to alleviate the symptoms of depression have been sought, for example, from nutritional research.

Vitamin D is believed to regulate central nervous system functions the disturbances of which have been associated with depression. In addition, cross-sectional studies have observed an association between depressive symptoms and vitamin D deficiency. However, previous meta-analyses on the effects of vitamin D supplementation on depression have been inconclusive. In a meta-analysis, results from several different studies are combined and analysed statistically.

The new meta-analysis on the association of vitamin D supplementation with depression is the largest one published so far, including results from 41 studies from around the world. These studies have investigated the efficacy of vitamin D in alleviating depressive symptoms in adults by randomised placebo-controlled trials in different populations. The studies included those carried out in patients with depression, in the general population, and in people with various physical conditions. The results of the meta-analysis show that vitamin D supplementation is more effective than a placebo in alleviating depressive symptoms in people with depression. There were major differences in the vitamin D doses used, but typically the vitamin D supplement was 50–100 micrograms per day.

“Despite the broad scope of this meta-analysis, the certainty of evidence remains low due to the heterogeneity of the populations studied and the due to the risk of bias associated with a large number of studies,” Doctoral Researcher and lead author Tuomas Mikola of the Institute of Clinical Medicine at the University of Eastern Finland says. The meta-analysis is part of Mikola’s PhD thesis.

“These findings will encourage new, high-level clinical trials in patients with depression in order to shed more light on the possible role of vitamin D supplementation in the treatment of depression,” Mikola concludes.

The meta-analysis was carried out in international collaboration between Finnish, Australian and US researchers.

DOI – 10.1080/10408398.2022.2096560 

“This research shows us that the brain is flexible and can take on additional burdens,” said David Richardson, an MD/PhD student in his fifth year in the Pathology & Cell Biology of Disease Program, and first author of the study recently published in the journal NeuroImage. “Our findings showed that the walking patterns of the participants improved when they performed a cognitive task at the same time, suggesting they were actually more stable while walking and performing the task than when they were solely focused on walking.”

During these experiments, researchers used a Mobile Brain/Body Imaging system, or MoBI, located in the Del Monte Institute’s Frederick J. and Marion A. Schindler Cognitive Neurophysiology Lab. The platform combines virtual reality, brain monitoring, and motion capture technology. While participants walk on a treadmill or manipulate objects on a table, 16 high speed cameras record the position markers with millimeter precision, while simultaneously measuring their brain activity.

The MoBI was used to record the brain activity of participants as they walked on a treadmill and were cued to switch tasks. Their brain activity was also recorded as they performed these same tasks while sitting. Brain changes were measured between the cued tasks and showed that during the more difficult the tasks the neurophysiological difference was greater between walking and sitting — highlighting the flexibility of a healthy brain and how it prepares for and executes tasks based on difficulty level.

“The MoBI allows us to better understand how the brain functions in everyday life,” said Edward Freedman, Ph.D., lead author on the study. “Looking at these findings to understand how a young healthy brain is able to switch tasks will give us better insight to what’s going awry in a brain with a neurodegenerative disease like Alzheimer’s disease.”

“Understanding how a young healthy brain can successfully ‘walk and talk’ is an important start, but we also need to understand how these findings differ in the brains of healthy older adults, and adults with neurodegenerative diseases,” said Richardson. “The next stage is expanding this research to include a more diverse group of brains.”

Additional authors include John Foxe, Ph.D., Kevin Mazurek, Ph.D., and Nicholas Abraham of the University of Rochester. This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Del Monte Institute for Neuroscience Pilot Program.

Journal Reference:

1. David P. Richardson, John J. Foxe, Kevin A. Mazurek, Nicholas Abraham, Edward G. Freedman. Neural markers of proactive and reactive cognitive control are altered during walking: A Mobile Brain-Body Imaging (MoBI) study. NeuroImage, 2022; 247: 118853 DOI: 1016/j.neuroimage.2021.118853

As background, the authors noted, “Recent evidence suggests that young women may be at higher risk of ischemic strokes than men of the same age. The goal of this systematic review is to reconcile and synthesize existing evidence of sex differences among you ng adults with ischemic strokes.

Through a database search of relevant studies, the investigators identified 16 eligible studies for the meta-analysis. The studies included a total international subject population of 69,793 young adults with stroke (33,775 women and 36,018 men).

They found that the largest difference by sex in the incidence of ischemic strokes was among subjects under 35, where 44% more women than men suffered ischemic strokes. This gap narrowed among subjects in the 35 to 45 age group.

The researchers concluded, “Traditional atherosclerotic risk factors are a major contributor to ischemic strokes in both young men and women and become increasingly important with age. However, these risk factors are less prevalent in younger women and may not account for the observed higher incidence of ischemic strokes in women younger than age 35. Young women who are survivors of ischemic stroke also have worse outcomes, with 2 to 3 times higher risk of poorer functional outcomes compared to their male counterparts.”

Co-author Sharon N. Poisson, M.D., associate professor of neurology at the University of Colorado, Denver, added, “Our finding suggests that strokes in young adults may be happening for different reasons than strokes in older adults. This emphasizes the importance of doing more studies of stroke in younger age groups so that we can better understand what puts young women at a higher risk of stroke.”

You’re startled by a threatening sound, and your breath quickens; you smash your elbow and pant in pain. Why a person’s breathing rate increases dramatically when they’re hurting or anxious was not previously understood. Now, a team of Salk scientists has uncovered a neural network in the brain that coordinates breathing rhythm with feelings of pain and fear. Along with contributions to the fields of pain management, psychological theories of anxiety, and philosophical investigations into the nature of pain, their findings could lead to development of an analgesic that would prevent opioid-induced respiratory depression (OIRD), the disrupted breathing that causes overdose deaths.

In the study published in Neuron, the Salk group focused on a group of neurons in the brainstem called the lateral parabrachial nucleus, which is arranged in a core-shell configuration. They found that neurons in the core project to the amygdala, an area of the brain that processes fear and the emotional experience of pain. Neurons in the shell project to the pre-Bötzinger complex, a region that generates breathing rhythm. The core and shell neurons influence each other according to inputs from these areas, making us breathe faster when we experience pain or anxiety.

“We are the first group to demonstrate how the lateral parabrachial nucleus coordinates breathing and pain,” says the paper’s senior author, Sung Han, assistant professor in Salk’s Clayton Foundation Laboratories for Peptide Biology. “By understanding the circuits in this brain region, we may be able to tease apart breathing regulation and pain regulation to develop a medication that inhibits feelings of pain without repressing breathing, like OIRD.”

In OIRD, opioids repress breathing as well as pain; it is the major cause of death from opioids. In previous work,Han’s lab showed that opiates like morphine repress breathing by triggering specific receptors, called mu opioid receptors (MOR), leading to the inhibition of neurons that express them. They also showed that reactivating the cells that express MOR can reverse OIRD. The current work suggests additional approaches for preventing OIRD, possibly by inhibiting neurons in the region’s core (blunting fear/anxiety) while exciting similar neurons in the shell (supporting breathing).

To show how these neurons coordinate breathing with pain and emotions, the researchers first used light and chemical agents to prove that manipulating the MOR-expressing neurons in the lateral parabrachial nucleus alters breathing rate in mice. They then used fluorescent tracers to map the inputs and outputs to the MOR-expressing neurons. Their results indicated that neurons clustered in the core of the region project to the central amygdala, while neurons clustered in the surrounding shell project to the pre-Bötzinger complex. Electrophysiological recordings of one population while stimulating the other population revealed that some of those subpopulations are reciprocally connected, with an excitatory network between them. Via this network, signals of fear and pain were coordinated with breathing rhythms.

“We have found very intricate circuits involving upstream and downstream input to these neurons. By uncovering this circuit mechanism, we can better explain why breathing can often be coordinated with pain and anxiety,” says first author Shijia Liu, a graduate student in Han’s lab.

Han is eager to see the team’s discovery have a translational application. “The biggest problem these days is that opioids reduce pain but also reduce breathing, so people die,” says Han, holder of the Pioneer Fund Development Chair. “By understanding those two mechanisms in our research, maybe we can manipulate certain populations of neurons by pharmacological intervention so that we can control pain without changing the breathing.”

Han’s group is currently working on genetic analyses of the core and shell population to identify functional markers that specifically regulate pain or breathing.

Other authors on the study are Mao Ye, Gerald M. Pao, Jinho Jhang, Jonghyun Kim, Sukjae Joshua Kang, Dong-Il Kim of Salk; and Samuel Myeongsup Song and Haibei Jiang of the University of California San Diego.

The research was supported by the National Institute of Mental Health, the Brain Research Foundation, the Mary K. Chapman Foundation, the Jesse & Caryl Philips Foundation, the National Institutes of Health-National Cancer Institute and the Waitt Foundation.

Journal Reference:

1. Shijia Liu, Mao Ye, Gerald M. Pao, Samuel M. Song, Jinho Jhang, Haibei Jiang, Jong-Hyun Kim, Sukjae J. Kang, Dong-Il Kim, Sung Han. Divergent brainstem opioidergic pathways that coordinate breathing with pain and emotions. Neuron, 2021; DOI: 1016/j.neuron.2021.11.029

Parkinson’s disease can progressively affect all movement including manual dexterity, speech, walking and balance due to a gradual reduction of a chemical in the brain called dopamine, a substance that helps control movement. Motor symptoms in the early stages of Parkinson’s disease include tremor, rigidity and bradykinesia, which is slowness of movement. To relieve these early symptoms, treatment options include dopaminergic medications, drugs that increase dopamine levels or mimic dopamine effects.

“We carefully reviewed the available research on the effectiveness and possible risks of medications to treat motor symptoms in people with early Parkinson’s disease and found that levodopa is usually the best first treatment for these symptoms,” said guideline lead author Tamara Pringsheim, MD, MSc, of the University of Calgary in Alberta, Canada, and a Fellow of the American Academy of Neurology. “Still, there are side effects with levodopa as well as other drugs, so it is important that a person newly diagnosed with Parkinson’s disease discusses all options with their neurologist before deciding on the best treatment plan for them.”

The guideline recommends that neurologists should counsel people with early Parkinson’s disease on the benefits and risks of initial therapy of the following three treatment options: levodopa, a drug that is converted into dopamine in the brain; dopamine agonists, drugs that mimic the effects of dopamine; and monoamine oxidase B (MAO-B) inhibitors, drugs that prevent an enzyme called MAO-B from breaking down dopamine.

The guideline states that medications may help alleviate motor symptoms.

According to the guideline recommendations, treatment with levodopa provides superior benefit at reducing motor symptoms when compared to treatment with either dopamine agonists or MAO-B inhibitors.

At the same time, the guideline also found that initial treatment with levodopa is more likely than initial treatment with dopamine agonists to cause dyskinesia—involuntary, erratic writhing movements of the face, arms, legs or trunk—during the first five years of treatment. But the prevalence of severe or disabling dyskinesia was also low during this time frame. The guideline recommends that neurologists prescribe the lowest effective dose of levodopa to optimize benefit and minimize the risk of dyskinesia.

While less likely to cause dyskinesia, the guideline found that dopamine agonists are more likely to cause impulse-control disorders such as compulsive gambling, eating, shopping or sexual activity, as well as hallucinations. They are also associated with a greater risk of excessive daytime sleepiness, so people with jobs that require driving or operating heavy machinery may face greater impairment from these side effects.

The guideline found that people are more likely to stop their treatment due to side effects when taking dopamine agonists and MAO-B inhibitors than when taking levodopa. It also found that people taking MAO-B inhibitors were more likely to require additional therapy within two to three years.

“Choosing to start a medication is a collaborative decision between a person with Parkinson’s disease, their neurologist, and their caregiver,” said Pringsheim. “The right medication will depend on a person’s symptoms, age and life circumstances. They are encouraged to discuss the potential benefits and adverse effects of medication options with their neurologist and care team.”

Learn more about Parkinson’s disease at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life^® on Facebook, Twitter and Instagram.

The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 36,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

“The human avoidance response to unpleasant smells associated with danger has long been seen as a conscious cognitive process, but our study shows for the first time that it’s unconscious and extremely rapid,” says the study’s first author Behzad Iravani, researcher at the Department of Clinical Neuroscience, Karolinska Institutet.

The olfactory organ takes up about five per cent of the human brain and enables us to distinguish between many million different smells. A large proportion of these smells are associated with a threat to our health and survival, such as that of chemicals and rotten food. Odour signals reach the brain within 100 to 150 milliseconds after being inhaled through the nose.

The survival of all living organisms depends on their ability to avoid danger and seek rewards. In humans, the olfactory sense seems particularly important for detecting and reacting to potentially harmful stimuli.

It has long been a mystery just which neural mechanisms are involved in the conversion of an unpleasant smell into avoidance behaviour in humans. One reason for this is the lack of non-invasive methods of measuring signals from the olfactory bulb, the first part of the rhinencephalon (literally “nose brain”) with direct (monosynaptic) connections to the important central parts of the nervous system that helps us detect and remember threatening and dangerous situations and substances.

Researchers at Karolinska Institutet have now developed a method that for the first time has made it possible to measure signals from the human olfactory bulb, which processes smells and in turn can transmits signals to parts of the brain that control movement and avoidance behaviour.

Their results are based on three experiments in which participants were asked to rate their experience of six different smells, some positive, some negative, while the electrophysiological activity of the olfactory bulb when responding to each of the smells was measured.

“It was clear that the bulb reacts specifically and rapidly to negative smells and sends a direct signal to the motor cortex within about 300 ms,” says the study’s last author Johan Lundström, associate professor at the Department of Clinical Neuroscience, Karolinska Institutet. “The signal causes the person to unconsciously lean back and away from the source of the smell.”

He continues:

“The results suggest that our sense of smell is important to our ability to detect dangers in our vicinity, and much of this ability is more unconscious than our response to danger mediated by our senses of vision and hearing.”

The study was financed by the Knut and Alice Wallenberg Foundation, the National Institute on Deafness and Other Communication Disorders and the Swedish Research Council. There are no reported conflicts of interest.

Journal Reference:

1. Behzad Iravani, Martin Schaefer, Donald A. Wilson, Artin Arshamian, Johan N. Lundström. The human olfactory bulb processes odor valence representation and cues motor avoidance behavior. Proceedings of the National Academy of Sciences, 2021; 118 (42): e2101209118 DOI: 1073/pnas.2101209118