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n The Chronicle is committed to maintaining leadership in environmentally sustainable policies, and to encouraging the adoption of “greenaware” practices in healthcare. We invite your comments via e-mail, at: health@chronicle.org

Editorial: New ‘useful’ concussion guidelines for athletes ..........3 Non-pharmacologic Tx showing promise for depression................7 New tool for screening for adult anxiety-related disorders ......14

Children with high-persistent SEPAD have lasting impacts Anxiety

Treating

n Increased depression, worse physical health

by Emily Innes-Leroux,

concussion in sports

please turn to page 12

Predictors: neurocognitive disorders

Managing Editor, The Chronicle

Ilgar Jafarov [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

All rights reserved. Chronicle Information Resources Ltd. Canada Post Canadian Publications Mail Sales Product Agreement Number 40016917

Canada’s National Newspaper of the CNS Sciences n December 2017

children with high-and-persistent separation anxiety disorder (SEPAd) followed in a longitudinal study into preadolescence were found to have a significant anxiety and depression symptoms, maternal panic disorder-agoraphobia (Pd-AgO), worse academic achievement, and worse physical health. The study, published in the journal Depression and Anxiety (Oct. 2017; 34:918– 927), also found that this population had an increase of RESCHOOl

P

AgEd

asthma-related conditions and pain—especially headaches. “I would like clinicians to consider separation anxiety with a broader view and a more longitudinal view. It is not something that is marginal, it is something that can be quite long-lasting and farfetching with important possible consequences to mental and physical health,” said study lead author dr. Marco Battaglia, associate chief of the division of Child & Youth Psychiatry at the Centre for Addiction and Mental Health in Toronto. —please turn to page 15

Review from ECTRIMS-ACTRIMS Paris 2017 The 7th joint ECTRIMS-ACTRIMS was held in Paris in Oct. MS

2017. Speakers at the conference reported late-breaking results from clinical trials on therapies for progressive MS and relapsing MS. The meeting also featured work by Canadian researchers in “Hot Topic” areas. —See page 10

Dementia

n Late-life emotional symptoms are a risk for cognitive decline by John Evans, Associate Editor, The Chronicle

arising later in life appear to have prognostic value for predicting the development of neurocognitive disorders, a finding investigators say should guide future study design as well as informing diagnosis. These findings come from a selective scoping review published in International Psychogeriatrics (Sept. 13, 2017, online ahead of print), which built on earlier research by members of the Neuropsychiatric Syndromes Professional Interest Area (PIA) group of the —please turn to page 8 MOTIONAl ANd AffECTIvE dYSREgulATION

E

This issue’s Chronicle Vitae profiles Dr. Karen Saperson, who received Founder status for the Geriatric Psychiatry subspecialty and was the 2017 recipient of the AMS/Donald R. Wilson Award. See page 18


F U N D I N G

R E S E A R C H

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H O P E

Epilepsy Canada is a proud partner to neurology professionals. For over 50 years, we have helped to fund epilepsy research at universities and hospitals across the country. To learn more about our program of student bursaries and Research Fellowships visit www.epilepsy.ca/research

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“As far as service goes, it can take the form of a million things.

To do service, you don’t have to be a doctor working in the slums for free, or become a social worker. Your position in life and what you do doesn’t matter as much as how you do what you do.” —Dr. Elisabeth Kübler-Ross, Swiss-American psychiatrist (1926-2004)

Guest editorial: New useful concussion guidelines for athletes lEAdER IN INjuRY PREvENTION,

PARACHuTE, has released the Canadian guideline on Concussion in Sport.1 More than 650 of every 100,000 Canadians each year sustain a concussion and the incidence is rising.2 Youth playing sports, such as hockey, football, and soccer, are particularly at risk. Of those who experience concussion, 25% have longer term problems with post-concussion symptoms such as debilitating headaches, cognitive difficulties and mood problems.3–5 As the information and management strategies given to patients and their families are highly variable and often conflicting, these Public Health Agency of Dr. Barlow Canada sponsored guidelines represent a significant step forward in concussion care.6,7 guidelines improve knowledge translation and management practices, especially when translated into care pathways.8,9 Ideally, they should be based on the latest evidence and expert opinion, be informed by patients and patient support groups, and be useful in a variety of settings.10,11 The 5th International Sport Concussion Consensus Statement released earlier this year forms the basis for these guidelines.12 Indeed, the guideline development team includes several of the experts who played a key role in the methodological rigour employed to develop that consensus statement.13

A

KEY STEPS IN EARLY ASSESSMENT OUTLINED Although this guideline is not a clinical pathway, key steps in the early assessment, decision-making, and guidance around return to normal activities following a concussion are outlined in the document. Seven areas are covered: pre-season education, head injury recognition, onsite medical assessment, medical assessment, early concussion management,

ABOUT THE AUTHORS Dr. Karen Barlow is an academic pediatric neurologist, clinical trialist, and specialist in acquired brain injury in children and adolescence. She was the founder and director of the Pediatric Acquired Brain Injury Rehabilitation program at the Alberta Children’s Hospital between 2002 and 2017. She then moved to the Child Health Research Centre at the University of Queensland, Australia in Oct. 2017. Dr. Barlow’s research focuses on the neurobiological signatures of subtle neurological dysfunction mainly in mild traumatic brain injury and concussion, especially the behavioural and cognitive impairments that are found in postconcussion syndrome (PCS). Photo of Dr. Barlow by Riley Brandt/University of Calgary

multidisciplinary concussion care and return to sport. The format is clear and concise, accentuating “who” the strategy is for and “how” the help is received. It contains many userfriendly tools such as the latest versions of the Concussion Recognition Tool, Sport Concussion Assessment Tools, Return to School and Return to Sport plans, which can be easily downloaded from the website www.parachutecanada.org.12 These guidelines and resources are useful for players and athletes as well as those with non-sport related concussion who have typical recovery patterns. Similar to the International Consensus statement, the role of rest is de-emphasized and the earlier graduated return to school and work encouraged, albeit conservative in its approach. Of course, underpinning this is the avoidance of repeat injury. When symptoms are prolonged (greater than two weeks in adults or four weeks in the child), early referral to more specialized care or involvement of a variety of professionals is encouraged as part of “the multidisciplinary team.” The implementation of any clinical guideline or care pathway is dependent on the infrastructure to support it. Particularly useful here are the written standardized instructions, ‘medical assessment’ and ‘clearance for return to play’ letters which can be downloaded and used to improve communication among patients, families, and professionals. unfortunately, access to the multidisciplinary services suggested for complex concussion care, especially those individuals with expertise in concussion, is limited for many Canadians. The guidelines attempt to address this by highlighting the allied health and education professionals such as clinical nurse specialists or practitioners, neuropsychology, mental health as well as education/employment specialists that can be useful for specific symptom management and re-integration into school and the workplace. The success of a guideline is determined by its net clinical benefit, such as consistent messaging, avoidance of repeat injury and complications, and improved recovery times.14 The next steps are for local health regions and policy drivers to use these guidelines as a springboard for the development of clinical care pathways tailored to the local population need, health care system and resources available. Implementation strategies incorporating research will be key when assessing the performance of these guidelines and resultant care pathways in order to assess their ability to reduce the burden of injury and improve the care of individuals sustaining concussion in Canada. —References on page 12

The Chronicle of Neurology & Psychiatry is published six times annually by the proprietor, Chronicle Information Resources Ltd., with offices at 555 Burnhamthorpe Rd., Ste. 306, Toronto, Ont. M9C 2Y3 Canada. Telephone: 416.916.2476; Fax. 416.352.6199. E-mail: health@chronicle.org. Contents © Chronicle Information Resources Ltd., 2017, except where noted. All rights reserved worldwide. The Publisher prohibits reproduction in any form, including print, broadcast, and electronic, without written permissions. Printed in Canada. Mail subscriptions: $72 per year in Canada, $125 per year in all other countries. Single copies: $12 per issue (plus 13% HST) Canada Post Canadian Publications Mail Sales Product Agreement Number 40016917 The Publisher certifies that advertising placed in this publication meets Revenue Canada requirements for tax deductibility. Volume 20, Number 5 published December 2017 ISSN 1209-0565

Research

n Researchers have developed a thera-

py called AVATAR, which is a treatment for people with schizophrenia who experience auditory hallucinations. The treatment allows patients to interact with a digital representation of their presumed persecutor. Voiced by the therapist, the avatar responds by becoming less hostile, conceding power over the course of therapy, according to a study published online ahead of print in The Lancet Psychiatry (Nov. 23, 2017). —Find more info at goo.gl/aW5yEg

n A long-term (96-week) study of

Botulinum Toxin Type A (BoNT-A) as monotherapy for essential tremor (ET), using kinematically driven injection parameters, was conducted by scientists in the U.K. Results showed that individualized BoNT-A dosing patterns to each individual’s tremor biomechanics provided an effective monotherapy for ET, as function improved without operationally limiting muscle weakness. The study was published online ahead of print in the Canadian Journal of Neurological Sciences (Nov. 21, 2017). —Discover more info at goo.gl/cNf3dE

n Using a sample of 893 placebo-

treated patients, a study concluded that older age at disease onset and lower functional scores, were associated with faster rate of slow vital capacity decline in patients with amyotrophic lateral sclerosis (ALS). Slow vital capacity change over time was associated with meaningful clinical events, including time to respiratory insufficiency or death in patients with ALS. This suggests that weakening of respiratory function, measured by slow vital capacity, is a key measure of clinical progression of ALS. The findings, published in the journal Neurology (Nov. 2017; 89(21):2136-2142), are a potentially useful end point in future ALS clinical trials. —Learn more at goo.gl/SjQjCw December 2017 n 3


s Atelier:

“There are millions of feelings I don’t even know, but I have no time to deal with it. Life is too busy to fall apart,” said a woman in her late 20s whose perfectionistic character can be seen in the art. This art represents solely one past relationship in which she could not come to terms with her pain. A lifeless rose representing herself reveals an emotional state of devastation. The broken glass points to a lack of safety. “Part of me feels numb. I can’t even relate to it. I have been sad, scared, and angry . . . I was inspired with an introduction to networking, to the world. Every happy moment was tainted . . . violent, and angry. I rarely stood up for myself as I was scared. I let someone in who controlled my life.” A hand on the left represents herself as a helpless bystander. “The most hurtful and difficult moment in my life is about how other people are controlling me.” —Keisei Yevonne Anzai, registered art therapist, Vancouver —More information at www.arttherapy.keisei-anzai.com

s Quick-start guide to The Chronicle, December 2017: Publication Index

n Depression: New options to manage treatment-resistant depression (p. 6) n Dementia: Modifying vascular risk factors could reduce dementia, Alzheimer’s disease risk (p. 9) n ECTRIMS-ACTRIMS: update from Paris 2017 MS meeting (p. 10) n Concussion: A new guideline for the diagnosis and management of suspected concussion sustained during a sporting activity (p. 12) n Anxiety: New tool for screening for anxiety disorders in adults (p. 14) n CV: Profile of dr. Karen Saperson who received the AMS/donald R. Wilson Award and founder status: geriatric Psychiatry (p. 18) Photo courtesy of CAMH

Founding Editor

Richard Gladstone, MD, FRCPC

Psychiatry Editor

J. J. Warsh,

MD, FRCPC

Sarah A. Morrow,

MD, FRCPC

Roger S. McIntyre,

MD, FRCPC

Neurology Editor

Editor, Innovation in the Mind Sciences Editorial Director

R. Allan Ryan Managing Editor

Emily Innes-Leroux Associate Editor

John Evans Assistant Editor

Bianca Quijano Publisher

Mitchell Shannon

Sales and Marketing

Peggy Ahearn Christine Witowych Operations, Manager

Cathy Dusome

Admistrative

Naomi Ahferom Comptroller

Rose Arciero

4 n December 2017

Images from the world of neurological and psychiatric medicine: We invite you to submit your photographs for THE CHRONIClE Of NEuROlOgY + PSYCHIATRY. Send original high-resolution (2 megapixels and higher) jPgs to: health@chronicle.org.

PRINCE HENRY OF WALES (Prince Harry) visited the Centre for Addiction and Mental Health (CAMH) in Toronto on Sept. 23, 2017 during the Invictus Games. The Games, founded by Prince Harry, encourages wounded, injured, or sick armed services personnel and veterans to take part in a variety of sports. Prince Harry met with CAMH’s CEO, Dr. Catherine Zahn, (left) and many of CAMH’s researchers to learn about their work. Of particular interest to the prince was research into the treatment and prevention of post-traumatic stress disorder (PTSD), because many of the Invictus Games’ athletes have PTSD from their military service.


“We are not getting our ulcers being chased by saber-[toothed] tigers, we’re

inventing our social stressors—and if some baboons are good at dealing with this, we should be able to as well. Insofar as we’re smart enough to have invented this stuff and stupid enough to fall for it, we have the potential to be wise enough to keep the stuff in perspective.” —Dr. Robert Sapolsky, U.S. neurobiologist and professor of neurosurgery

Father’s depressive Brain plasticity in the frontal cortex symptoms impact significantly impaired in AD patients adolescent’s mood n Brain plasticity could be future target for treatment, prevention

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exhibit depressive symptoms are at an elevated risk of experiencing symptoms of depression themselves, revealed results from a study of two population-based cohorts (Lancet Psychiatry dec. 2017; 4(12):920-926). The authors noted that while a link between maternal depression and children’s risk of depressive symptoms has been established in the literature, the association between depression in fathers and their adolescent children, independent of whether the mother has depression, is less understood.

PARENT GENDER NOT A FACTOR IN CHILD DEPRESSION RISK “There’s a common misconception that mothers are more responsible for their children’s mental health, while fathers are less influential—we found that the link between parent and teen depression is not related to gender,” said the study’s lead author, dr. gemma lewis, a lecturer in the division of Psychiatry, faculty of Brain Sciences, university College london, u.K., in a press release. data for two-parent families was taken from two representative prospective cohorts from Ireland and the u.K. This totalled 6,070 and 7,768 families, respectively, for the two cohorts. In the cohorts, parental depressive symptoms were assessed via questionnaire when the children were nine and seven years old in the two cohorts. Adolescent depressive symptoms were assessed when the children were 13 and 14 years old. After adjusting for confounding factors—including maternal depression—the investigators found that for every three-point increase on the Mood and feelings Questionnaire (MfQ) score on the part of fathers, there was an associated 0.2-point increase in the children’s MfQ score. These findings were seen in both study samples. The strength of the association is comparable to what is seen between mothers with depression and their children, the authors noted. —Read more information at goo.gl/PsH4Kr

n A full-scale randomized trial

prefrontal cortex plasticity is impaired in patients with Alzheimer’s disease (Ad), according to a cross-sectional study published in JAMA Psychiatry (dec. 2017; 74(12):1266-1274). The findings, according to a press release, provide a new focus for exploring ways to treat or prevent dementia. The investigators also reveal that people with reduced plasticity in the frontal Don Palmer, a research volunteer, and Apoorva Bhandari, lobes also experienced research analyst in Geriatric Psychiatry at CAMH, demonstrate the CAMH-developed approach to study brain plasticipoorer working memory. “What’s exciting is ty in the frontal lobes. that we clearly demonbrain plasticity in the frontal lobes. strated impairments in brain plasticity in In the CAMH-developed approach, the frontal lobes in people with early the researchers use scalp electroenAlzheimer’s disease, and we showed that cephalography (EEg), which measures impaired brain plasticity is related to electrical output generated directly by the impaired function of the frontal lobes, frontal lobes in response to two-pronged specifically working memory,” says dr. brain stimulation, referred to as paired Tarek Rajji, senior author of the study and associative stimulation (PAS). The particichief of the Adult Neurodevelopment and pant wears a 64-node cap that transmits the geriatric Psychiatry division at the Centre EEg signal, and researchers measure a perfor Addiction and Mental Health son’s EEg signal before and after stimula(CAMH). “This may indicate that impairtion. Changes in this signal are an indicator ments in brain plasticity underlie impairof brain plasticity in the frontal lobes. ments in memory.” The study included 32 people with The findings are promising because Ad and 16 healthy individuals, aged 65 “impaired brain plasticity may be a future years or older. “In both healthy individutarget for treatment or prevention of als and people with early Alzheimer’s disdementia, for which no great treatments ease, we were able to illicit a plasticity exist at present,” says dr. Sanjeev Kumar, response from the frontal lobes, which is lead author of the study and medical head positive in that it shows that the brain cirof geriatric Mental Health Inpatient cuits are still working in people with early Services at CAMH. Alzheimer’s disease,” says dr. Kumar. “But plasticity was significantly lower in PLASTICITY ASSOCIATED WITH people with Alzheimer’s disease.” COGNITIVE RESERVE Prior to the PAS arm of the study, Healthy plasticity in the frontal lobes is important because researchers believe this each participant completed a memory test brain region supports the brain’s cognitive to assess their ability to recall alphabetic reserve that offsets poorer functioning in letter sequences. Individuals with impaired other brain areas that may contribute to the plasticity also had poorer recall ability. As next steps, the researchers are development of dementia. “Individuals with a higher reserve have been shown to investigating approaches to enhance plasdevelop dementia later in life than those ticity in the frontal lobes. This includes research on brain stimulation alone or with a lower reserve,” says dr. Kumar. The research team used an innova- combined with brain-training exercises. —Find more information at tive approach, developed by dr. Rajji and goo.gl/WV1Gb7 his colleagues in earlier research, to study ORSOlATERAl

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Photo courtesy of CAMH

dOlESCENTS WHOSE fATHERS

In the news . . . showed that venous percutaneous transluminal angioplasty (PTA) did not slow multiple sclerosis (MS) progression, nor did the therapy significantly reduce the appearance of new brain lesions. The study was conducted to test the controversial theory that inadequate blood flow in the central nervous system (called chronic cerebrospinal venous insufficiency or CCSVI) is a potential cause of MS. The researcher who first used PTA as a treatment for CCSVI, Paolo Zamboni, PhD, concluded that no further doubleblinded clinical trials are needed and that the treatment cannot be recommended for patients with MS, according to a report by the Chicago Tribune (Nov. 29, 2017). —Find more information at goo.gl/SjQjCw

n A recent study from University

College London suggests that people who are single for the remainder of their lives increase their risk of developing dementia by 42%, in comparison with married couples. Conversely, people who have been widowed have a 20% increased chance of being diagnosed with dementia. The researchers analyzed 15 separate studies to evaluate 800,000 people worldwide, reports The Independent (Nov. 29, 2017). —Read this article at goo.gl/QiuJhb

n Screen time is linked to depression

in teens, according to a San Diego State University survey of 500,000 adolescents aged 13 to 18 years. The report found that almost 50% of teens who spent five or more hours looking at electronic devices per day had depressive symptoms. In comparison, only 28% of teens who spent less than one hour per day looking at screens reported signs of depression, reports The Chronicle Herald (Nov. 27, 2017). —Read more at goo.gl/wDW3YC December 2017 n 5


New options to manage treatment-resistant depression

n Presenters at the CPA meeting discuss pharmacotherapy, non-pharmacologic therapies

by Louise Gagnon,

Correspondent, The Chronicle

t IS IMPORTANT fOR ClINICIANS TO IdENTIfY depression that is truly resistant to pharmacotherapy, and refrain from diagnosing depression as resistant to treatment in patients who are not compliant in taking their medication. “There is true resistance, where people are compliant, and do not get better,” said dr. Arun v. Ravindran, professor, department of Psychiatry, university of Toronto, in an interview with THE CHRONIClE. “The other is pseudo-resistance, where patients are not compliant, and they do not tell you that they are not compliant, and they say they are not getting better.” Some of the reasons for non-compliance to pharmacotherapy for the treatDr. Ravindran ment of depression include either the experience of adverse events or the fear of adverse events, said dr. Ravindran. Along with other clinicians, dr. Ravindran discussed advances in the management of treatment-resistant depression in Ottawa during the annual meeting of the Canadian Psychiatric Association (CPA) in September. dr. Ravindran suggested that complementary and alternative medicines can be adjunctive to pharmacotherapy. “If patients are unable to tolerate optimal doses of medication, they can augment with [complementary and alternative medicines].” There are various levels of evidence for modalities such as diet modification, exercise, and yoga, noted dr. Ravindran. None of these modalities, however, are appropriate as monotherapy to manage moderate-to-severe depression, he stressed. Omega-3 fatty acids are found in foods like oily fish and some nuts and seeds, and the 2016 Canadian Anxiety for Mood and Anxiety Treatments (CANMAT) guidelines suggest diet supplementation with omega-3 fatty acids as second-line therapy, either as monotherapy or adjunctive therapy, for mild-to-moderate depression. According to the guidelines, exercise can be first-line therapy and monotherapy for mild-to-moderate depression. The CANMAT guidelines suggest yoga as a second-line treatment for mild-to-moderate depression and that it has an adjunctive role in treating that degree of depression.

I

NOVEL PHARMACOLOGIC APPROACHES Clinicians are looking at augmenting antidepressant therapy with the addition of an atypical antipsychotic such as aripiprazole or brexpiprazole, noted dr. Roumen Milev, professor of Psychiatry and Psychology, head, department of Psychiatry, Queen’s university, Kingston, Ont. dr. Milev, who co-chaired the symposium on advances in the management of treatment-resistant depression at the CPA, pointed to newer antidepressants that include levomilnacipran (a serotonin-norepinephrine reuptake inhibitor) and vortioxetine (a serotonin modulator) that clinicians can consider if more conventional antidepressants, like selective serotonin reuptake inhibitors (SSRIs), do not produce a response and/or are unable to achieve remission. 6 n December 2017

One novel pharmacotherapy that is being explored to treat depression is ketamine, although it is not indicated for depression. despite not having this indication, ketamine is finding its way into clinical practice, noted dr. Milev. “It is a medication that is approved in Canada and has been used for many years [as an anesthetic],” said dr. Milev. “We would [usually] give lower doses than [are given] in anesthesia.” Ketamine, which has a different mechanism of action from SSRIs—medications which have been widely prescribed to treat depression—will be explored as a treatment for depression in clinical investigations at several Canadian sites. It will be delivered intranasally, offering an alternative to intravenous infusion, a more invasive route of administration that is also more timeconsuming for patients and clinicians alike. With the intranasal route of administration, however, patients would still have to be monitored, as they would if exposed to ketamine via intravenous infusion. A recently published systematic review and meta-analysis found that a single dose of intravenous ketamine rapidly decreased suicidal ideation, highlighting Dr. Milev the efficacy of the agent in severe depression (Am J Psychiatry 2017 Oct. 3). A general rule in depression management is that depression becomes more treatment-resistant the longer that it remains untreated, underlining the importance of early treatment. “depression needs to be treated,” urged dr. Milev. “The longer you leave it untreated, the worse the outcome. It is like a broken bone. It needs to be fixed. It does not matter how the bone became broken.”

NO ROLE FOR CANNABIS, ALCOHOL, OR TOBACCO Some individuals are more vulnerable to developing depression, and exogenous exposure to stressors like alcohol and cannabis may contribute to the risk of depression in these individuals, according to dr. Milev. “We advise against the use of marijuana in depression,” he said. “Some people report anecdotally that they become better, but it is not scientifically proven. It’s not recommended as a treatment for depression. We also advise modifying the consumption of alcohol, to try to reduce or minimize or eliminate the use of it.” dr. diane McIntosh, psychiatrist and clinical assistant professor at the university of British Columbia in vancouver, expressed concern about adolescents using cannabis to treat their depression, for these are individuals whose brains are in development. “There is an effect on the developing brain,” said dr. McIntosh. “There’s a risk in promoting onset of psychosis in the vulnerable brain. There is no evidence for it being an alternative treatment for depression.” Similarly, tobacco use has not been shown to offer benefit in managing depression. “There’s no evidence that tobacco smoking helps patients treat their depression,” she said. Non-proprietary and brand names of therapies: aripiprazole (Abilify, Bristol-Myers Squibb Canada); brexpiprazole (Rexulti, Otsuka Pharmaceutical); levomnilnacipran (Fetzima, Allergan).


Non-pharmacologic treatments showing promise for treating depression n Potential for light therapy to treat non-seasonal depression; rTMS and MST for medication-resistant depression

by Louise Gagnon,

Correspondent, The Chronicle

CANAdIAN PSYCHIATRIC Association annual meeting in Sept. 2017 in Ottawa outlined some advances in non-pharmacologic therapies that can be used adjunctively with pharmacologic therapy to treat depression. “light therapy is widely accepted as a first-line treatment for seasonal depression,” explained dr. Raymond lam, professor and BC leadership Chair in depression Research and associate head for Research department of Psychiatry, university of British Columbia in vancouver. “In the past few years, there has been a focus on looking at non-seasonal depression.” Dr. Lam Research has mainly supported the use of light therapy as an adjunct to medications, said dr. lam, also the director of the Mood disorders Centre at the djavad Mowafaghian Centre for Brain Health and executive chair, Canadian Network for Mood and Anxiety ATA PRESENTEd AT THE

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Treatments. “Many studies have shown that combining light therapy with antidepressants has positive effects,” he said. “It’s hard to know how effective [light therapy] is as monotherapy.” The exact mechanism of action of light therapy is not known, but dr. lam explained that light is thought to target neurotransmitters such as serotonin and dopamine, similar to how antidepressant medications work. One of the major advantages of light therapy is that it does not present a risk of toxicities. “light therapy has very few side effects and can be used safely with other treatments,” said dr. lam. THE CHRONIClE’s Psychiatry Editor, dr. jerry Warsh, noted that bright light therapy can induce hypmania/mania in bipolar depressed patients. “Also, there is a potential risk of accelerated retinal damage for depressed patients who have some subtypes of retinopathy (e.g., Stargardt’s disease).”

LIGHT THERAPY CONVENIENT FOR PATIENTS Another advantage is that it is a modality that conveniently fits into a patient’s daily life. “You can do it for 30 minutes in the morning while you do things like eat breakfast, or work on your laptop, or read,” said dr.

lam. Medications that typically have been used in combination with light therapy include selective serotonin reuptake inhibitors. Most commonly, sertraline and fluoxetine have been combined with light therapy. light therapy is also demonstrating benefit in an adjunctive capacity to treat bipolar depression. Recently published data from a randomized, double-blind, placebo-controlled trial found patients with bipolar disorder and major depressive episodes, and who were being treated with mood stabilizing medication, benefitted from exposure to light therapy at midday. The patients who received light therapy in the trial experienced significantly lower depression scores compared to their counterparts treated with a placebo (Am J Psychiatry Oct. 2017). light therapy is also being investigated in patients who are cognitively impaired and who are typically elderly. A meta-analysis of randomized, controlled trials found light therapy was able to relieve behavioural disturbances, sleep quality, and depression (J Am Geriatr Soc Oct. 2017; 65(10):2227–2234). Another non-pharmacologic option to treat depression includes —please turn to page 17

Similar cortical thickening in insular cortex found in patients with MDD and SAD

RESEARCHERS USING MRI have discovered a common pattern of structural abnormalities in brains of people with major depressive disorder (MDD) and social anxiety disorder (SAD). The study was presented at the annual meeting of the Radiological Society of North America and published in the journal EBioMedicine (July 2017; 21:228-235). “Our findings provide preliminary evidence of common and specific grey matter changes in MDD and SAD patients,” said study author Dr. Youjin Zhao, with The Institute of Huaxi MR Research Center (HMRRC) of West China Hospital of Sichuan University, in a press release. “Future studies with larger sample sizes combined with machine learning analysis may further aid the diagnostic and prognostic value of structural MRI.” Thickness of the cortex was assessed using highresolution images from 37 MDD patients, 24 SAD patients, and 41 healthy control individuals. The differences between the MDD and SAD patients and the healthy controls related to either thickening or

thinning of the cortex in areas such as the orbitofrontalstriatal-thalamic circuit, salience network, and dorsal network. For instance, both MDD and SAD patients, compared with healthy controls, showed cortical thickening in the insular cortex. The relationship between clinical diagnosis of MDD and SAD and cortical thickening in these brain regions are unclear. Increased cortical thickness may be a result of a compensatory mechanism related to inflammation or other aspects of the pathophysiology, according to the investigators. It may also be a manifestation of continuous coping efforts and emotion regulation attempts by the patients. Involvement of the precentral cortex in patients with SAD and participation of the visual recognition network in

patients with MDD was also observed. Transformation of the visual recognition network might be related to impaired selective attention and working memory in MDD. “The visual recognition network is involved in emotional facial processing, which is crucial for social functioning,” said Dr. Zhao. “Depression has been associated with structural alterations in these regions.”

—Read more information at goo.gl/37hKCE December 2017 n 7


Late-life affect may be linked to neurocognitive disorders

—Continued from page 1

sure that neurocognitive or neurodegenerative diseases are part of that [differential diagnosis].”

International Society To Advance Alzheimer’s Research and Treatment (ISTAART), said lead author dr. Zahinoor Ismail, MORE DISTINCT STUDY POPULATIONS HELP RESEARCH in an interview with THE CHRONIClE Of NEuROlOgY + from a research standpoint, the review findings support the PSYCHIATRY. idea that the current diagnostic and Statistical Manual of “About five years ago, we met to Mental disorders (dSM-5) criteria is not equipped to separate develop, in a more concrete fashion, crite- late-onset symptoms, which may be MBI, from other neuria to describe what we saw clinically— ropsychiatric conditions, said dr. Ismail. that the emergence of neuropsychiatric “In our dSM framework, we have not attended to natural symptoms in history of neuropsychiatric symplate life often toms, especially the age of onset of presage demensymptoms. Because we have not Dr. Ismail tia,” said dr. In our DSM framework, we attended to that detail, our literature Ismail, who is an associate professor is really very inconsistent on what have not attended to natural at the Hotchkiss Brain Institute and [mild behavioural impairment] a clinician scientist in the Cumming history of neuropsychiatric means.” School of Medicine at the university for example, he said, studies symptoms, especially the of Calgary. They proposed research of depressive or anxiety symptoms criteria and named the syndrome age of onset of symptoms. are typically cross-sectional or peri‘mild behavioural impairment’ od prevalence studies, and “we do Because we have not (MBI). After a literature review and not really differentiate if they had an iterative refinement process, the their first episode when they were attended to that detail, our criteria were published in an open19, or 31, or 55, or 68 [years of access form last year in the journal literature is really age].” Alzheimer’s & Dementia (feb. 2016; “Similarly, if people develop very inconsistent on what 12(2):195–202). depressive symptoms that are subThe idea behind the new syndromal or sub-clinical, we do [mild behavioural paper was two-fold, said dr. not necessarily know how to capimpairment] means. Ismail. first, they aimed to expand ture that.” on the relation between emotional looking to the future of neu—Dr. Zahinoor Ismail, an associate professor dysregulation and cognitive decline rocognitive disorder research, dr. at the Hotchkiss Brain Institute and a in a way they could not in the origIsmail said the key will be to more clinician scientist in the Cumming School inal paper. Second, “lay the sort of clearly identify populations to of Medicine at the University of Calgary. ground work, and frame the sort study. of questions that need to be “If we are going to try to assess answered in a way that will hopefully incite clinicians and the neurobiology, the neuroimaging structures, the connectivity, researchers around the world to look at this in a systematic and the biomarkers of these [neurocognitive] illnesses, we really way. [for researchers] to participate in research and develop need to make our groups more homogenous—to increase the sigtheir own trials and protocols using this framework, mov- nal to noise ratio.” using natural history of disease to cluster ing forward.” patients by age of onset will allow researchers to draw from more He notes that there have been more than one hundred distinct populations rather than including, for example, everyone disease-modifying trials for dementia that have failed and a with depressive symptoms, he said. common explanation for failure for medications to separate NEW MBI CHECKLIST TO AID SYMPTOM IDENTIFICATION from placebo is that patients are being captured too late in To provide a tool to aid in distinguishing MBI from other contheir disease course. Being able to identify patients before cogditions, dr. Ismail and his colleagues published an MBI checknitive symptoms appear, possibly through signs such as affeclist in The Journal of Alzheimer’s Disease in jan. 2017, which is tive or emotional dysregulation, would be beneficial for available free online at www.MBItest.org. research and clinically, he said. “The development of the MBI checklist was in response FIRST ONSET OF SYMPTOMS WARRANT ATTENTION to a gap in our ability to [effectively] characterize, measure, dr. Ismail and his colleagues reviewed the existing litera- and describe mid- and late-life onset of neuropsychiatric ture in prodromal and dementia states, with a focus on epi- symptoms that did not necessarily fit formally into our current demiology and neurobiology. They found that affective psychiatric nosology,” he said. and emotional dysregulation are common in preclinical Having this checklist may also allow for more widespread and prodromal dementia syndromes, and are often early data capture, according to dr. Ismail. signs of neurodegeneration and progressive cognitive “You cannot do detailed gait assessments, or neuroimagdecline. ing, or audiometry on every person who walks through a famThe clinical take-away from these findings, he said, is: ily doctor’s office,” he said. “But it is very simple to administer “When clinicians see emergent symptoms in later life, they a seven-minute rating scale that is completed by [the patient’s] really need to broaden their differential diagnosis and make family member.”

8 n December 2017


Modifying vascular risk factors could reduce dementia, Alzheimer’s disease risk n Following American Heart Association’s “Life’s Simple 7” guidelines could have potential to reduce risk for developing dementia

by Emily Innes-Leroux,

vascular risk factors through lifestyle changes could lead to a reduction in dementia and Alzheimer’s disease risk, according to a presenter at the 9th annual Canadian Conference on dementia held in Toronto in Nov. 2017. “I think we are in an interesting era now,” said dr. Charles deCarli, victor and genevieve Orsi Chair in Alzheimer’s Research and director of the Alzheimer’s disease Center at the university of California: davis in davis, Calif. “We might be able to offer our patients and ourselves healthier brains through living what is going to be called ‘life’s Simple 7.’” vascular pathology commonly accompanies Ad and dementia, said dr. deCarli. He highlighted that vascular risk factors and vascular disease is common with the aging process and can lead to subclinical brain injuries and an increased risk for dementia. dr. deCarli started his presentation by highlighting research he conducted with the “framingham Heart Study Offspring Cohort” (Neurobiol of Aging 2005). The framingham Heart Study began in 1948 by recruiting an original cohort of 5,209 men and women between the ages of 30 and 62 years from framingham, Mass. who had not yet developed overt symptoms of cardiovascular disease or had a heart attack or stroke. Since that time the study has added an Offspring Cohort in 1971, the Omni Dr. DeCarli Cohort in 1994, a Third generation Cohort in 2002, a New Offspring Spouse Cohort in 2003, and a Second generation Omni Cohort in 2003.

Copyright American Heart Association

Managing Editor, The Chronicle

dENTIfYINg ANd TREATINg

I

VASCULAR RISK FACTORS ARE COMMON vascular risk factors were prevalent in the framingham Offspring Cohort when they were at a mean age of 62 years (±10 years). Thirty-three per cent were obese, 52% were hypertensive, 13% were diabetic, and 14% were smokers. This is reflective of the general population, though dr. deCarli noted that the rates of smoking and diabetes are a bit lower in the framingham cohort. “The point [of discussing this data] is to remind everyone that [vascular risk factors] are a common phenomenon,” said dr. deCarli. Ad risk scores have been well studied, said dr. deCarli. He highlighted dr. Miia Kivipelto’s (Aging Research Center, Karolinska Institutet, Stockholm) work in which it was concluded that “dementia risk score is a novel approach for the prediction of demen-

tia risk . . . [and] this approach highlights the role of vascular factors in the development of dementia” (Lancet Neurol 2006; 5:735–741). “[dr.] Rachel Whitmer replicated these findings in California using the Kaiser [Permanente] research in a much larger group [and] finds exactly the same thing. [She found . . . ] a linear increase in risk related to the score and again has vascular risk factors as part of this: weight, cholesterol, and hypertension [were] some of [the] major risk factors [for dementia]” (Neurology jan. 2005; 64(2):277–281).

SMOKING, HYPERTENSION ASSOCIATED WITH AD In their study of 721 participants with dementia, dr. Whitmer and colleagues found that smoking, hypertension, high cholesterol, and diabetes at midlife were each associated with a 20 to 40% increase risk in dementia. A composite cardiovascular risk score was created using all four risk factors and was associated with dementia in a dose-dependent fashion. Compared with participants having no risk factors, the risk for dementia increased from 1.27 for having one risk factor to 2.37 for having all four risk factors (fully adjusted model: HR 2.37, 95% CI 1.10 to 5.10). dr. Whitmer’s findings, according to dr. deCarli, were in a population of primary Caucasian participants, but these findings have been replicated in a study with participants from northern Manhattan, N.Y. with Caucasians, Hispanics, and African-Americans (Neurology Aug 2005; 65(4):545–551). The investigators noted that they included ethnic groups and education as covariates “because Hispanics and African-Americans, and subjects with lower years of education have a higher prevalence of vascular risk factors and also a higher risk of Ad.” To demonstrate the vascular risk factors association

with autopsy-confirmed Ad, dr. deCarli presented research conducted by dr. julie Schneider, professor of pathology and neurological sciences and associate director of the Alzheimer’s disease Center at Rush university in Chicago. Her autopsy study found that “vascular and Ad phenotypes overlap, such that the pathologic basis for dementia may not be easily extricated when there are mixed pathologies . . . Macroscopic infarcts and amyloid angiopathy have prominent effects on perceptual speed, but may also affect episodic memory, the phenotypic hallmark of clinical Ad” (Stroke Oct. 2010; 41(10 Suppl):S144-S146). “What this says to me is that we have a very common disorder of vascular risk factors . . . and that they add up and that at death they often co-occur with Alzheimer’s disease,” said dr. deCarli. He noted that the presence of silent cerebral brain infarcts can be observed in life using MRI-imaging and in the framingham Offspring group he found that the prevalence of brain infarcts increases with age. White matter disease (white matter hyperintensity volume) increased a bit with aging, but significantly more as vascular risks increased. “This leads me to conclude that maybe there is something going on with our vascular risks that then lead to some subtle vascular brain injury that is maybe affecting the brain [long] before you get amyloidosis. So just like APoE4 (Apolipoprotein E), these vascular factors may actually be risks for dementia,” said dr. deCarli. dr. deCarli believes that making life changes that reduce vascular disease will have an impact on reducing dementia/Ad, and research has begun to confirm his theory. An epidemiological review found that a 10 to 25% —please turn to page 17 reduction in seven modiDecember 2017 n 9


Update: ECTRIMS-ACTR rophy compared to placebo (p=0.04), as measured by MRI analysis using brain parenchymal fraction in patients with progressive MS.

by Emily Innes-Leroux,

Managing Editor, The Chronicle HE 7TH jOINT

ECTRIMS (European Committee for Treatment and Research In Multiple Sclerosis)-ACTRIMS (Americas Committee for Treatment and Research In Multiple Sclerosis) was held in Paris in Oct. 2017. Speakers at the conference reported late-breaking results from clinical trials for therapies such as ibudilast for progressive multiple sclerosis (MS) and ozanimod for relapsing MS. The meeting also featured work by Canadian researchers in “Hot Topic” areas such as cognition and cognitive remediation in multiple sclerosis (MS) and gut microbiota in MS. dr. Robert j. fox, managing director of the NARCOMS MS Patient Registry and staff neurologist at the Mellen Center for Multiple Sclerosis and vice-chair for Research of the Neurological Institute, Cleveland Clinic in Cleveland, presented findings from the recently completed SPRINT-MS/NN phase II trial of ibudilast in progressive MS during the “late Breaking News” session. Ibudilast, a phosphodiesterase- and macrophage inhibitory factor-inhibitor, which has been suggested to have a neuroprotective effect in relapsing-remitting MS, was found to provide a 48% reduction in the rate of progression of whole brainat-

T

IBUDILAST FOR PROGRESSIVE MS The investigators reported that there were no opportunistic infections, no cancers, no cardiovascular events, and no deaths related to ibudilast treatment. As well, there was no statistically significant difference in tolerability between the ibudilast group and the placebo group. “Ibudilast demonstrated a robust reduction in the rate of progression of whole brain atrophy, which is considered an important Phase 2 outcome measure in progressive MS. In addition, ibudilast appears to have a favourable safety and tolerability profile, which is just as important in developing therapies for progressive MS,” said dr. fox, in a press release. dr. Barry Singer, a St. louis-based neurologist, said that since there are limited treatment options for progressive MS, these results are promising. “There is a lot of optimism in trying to treat progressive disease,” he said, during a video interview with an MS Community reporter. “People have hope that we can change the disease course.”

OZANIMOD FOR RELAPSING MULTIPLE SCLEROSIS Results from the trial titled: “Ozanimod vs. interferon β-1a: clinical and MRI results of RAdIANCE part B—A 2-year Phase 3 trial in relapsing multiple sclerosis”, were also highlighted during the “late-Breaking News” session. This study was the companion study to the SuNBEAM trial. “We think the efficacy and safety results, combined with the positive results from the SuNBEAM trial, demonstrate a favourable benefit-risk profile for ozanimod in relapsing MS,” said dr. jeffrey A. Cohen, director of Experimental Neurotherapeutics at the Cleveland Clinic Mellen Center for Multiple Sclerosis and lead trial investigator, during his presentation. In this multicentre, randomized, double-blind, parallel-group, active treatmentcontrolled trial, 1,313 patients were randomized into three study arms: daily oral ozanimod 1 mg, daily oral ozanimod 0.5 mg, or weekly IfN β-1a injections. The primary end-point was annualized relapse rate, and key secondary endpoints included MRI assessments to measure T2 lesion changes and gadolinium enhancing (gdE) T1 lesions. The investigators reported a 38% reduction of annualized relapse rate in the ozanimod 1 mg group. The investigators also reported a reduction of new or enlarging T2 lesions and the number of the gdE lesions in the

New self-monitoring tools for patients with MS could help improve outcomes

SELF-MONITORING COULD RESULT IN BETTER PATIENT measurements, and ultimately improved outcomes in patients with multiple sclerosis (MS), according to a “Hot Topic” speaker at the 7th annual ECTRIMS-ACTRIMS conference in Paris in October. “There is no doubt when you give patients the power to monitor their own outcomes and change their treatment based on their outcomes, it improves what happens to them in the long term,” said Dr. Gavin Giovannoni, professor of neurology at Barts and The London in the U.K. He noted that outcomes have been improved for diabetes patients when they can self-monitor their glucose levels and improvements have also been achieved in anticoagulant clinics. “I think the same could happen in MS, we just need to give them the right tools,” said Dr. Giovannoni. He conducted a survey in which he found the majority of MS patients want to self-monitor. Patients are interested in self-monitoring because information is currently controlled by healthcare providers. A survey conducted by Dr. Giovannoni found that many clinicians do not complete Expanded Disability Status Scale (EDSS) scores, but also that those who do often miscalculate the scores (Schmierrer K, et al: Association of British Neurologists 2014; unpublished). Yet, EDSS scores are needed for many of the online self-monitoring prognostic calculators that have emerged online. “If the community wants to [engage] patients to understand their own disease we have to provide them with the metric to do it,” he said. 10 n December 2017

CLINIC SPEAK ONLINE TOOLS 1) The patient-reported online EDSS assessment is available at Dr. Giovannoni’s website Clinic Speak (http://www.clinicspeak.com/), which takes five to 10 minutes for patients to complete and obtain their own EDSS scores. 2) Access to a cardboard 9 Hole Peg Test is also available online at Clinic Speak (CAN$17) for patients to be able to calculate their own 9 Hole Peg Test scores. According to Dr. Giovanni, the cost of the traditional plastic peg test is prohibitive. The cardboard version of the test was validated in a study comparing it to the plastic version (Mult Scler Relat Disord. Oct. 2017; 17:172–176), and the investigators concluded that “the cardboard version is at least equivalent to the plastic version of the test with arguably better design attributes, making it the preferred option for self-monitoring.” “Preserving arm and hand function is critical for people with MS to remain independent and to preserve their quality of life,” Dr. Giovanni says on his website. “Although diseasemodifying therapies (DMTs) may not be able to preserve lower limb function in people with MS who already have pre-existing walking problems, we [hypothesize] that some DMTs may be able to preserve arm and hand function. Therefore, we are striving for future trials of new and existing DMTs to focus on arm and hand function.” Dr. Giovanni and colleagues have started a social media campaign called #ThinkHand to encourage more research regarding arm and hand function in patients with MS. 3) An online Timed 25-foot Walk tool is also available at Clinic Speak, which allows patients to determine their own Timed 25-ft Walk score. The website also features an instructional video for patients.


ozanimod groups. The ozanimod groups also had a slowing in whole brain volume loss, cortical grey matter volume loss, and thalamic volume loss. dr. Cohen reported that ozanimod was well tolerated and that serious adverse events were uncommon and balanced across the treatment arms. Results from the SuNBEAM trial were presented at ECTRIMS-ACTRIMS by dr. giancarlo Comi, department of Neurology, Scientific Institute H.S. Raffaele, Milan. dr. Comi said that ozanimod has selective targeting of the S1P Receptors 1, which has an impact of regulating the traffic of lymphocytes, and S1P Receptors 5. The investigators had also reported in this trial that both ozanimod 0.5 and 1 mg treatment groups demonstrated statistically significant reductions compared to IfN β-1a in annual relapse rate.

HOT TOPIC: COGNITION AND COGNITIVE REMEDIATION IN MULTIPLE SCLEROSIS Canadian clinician dr. Anthony feinstein presented during the “Hot Topics: Cognition and Cognitive Remediation in Multiple Sclerosis” session on mood disorders and affect in MS. dr. feinstein is a professor of psychiatry at the university of Toronto and an associate scientist at Sunnybrook Health Sciences Centre. “depression is a big problem in people with MS—the lifetime prevalence can approach 50 per cent in clinical populations,” said dr. feinstein. “If you look at the 12month prevalence, it is about 15 per cent, which is double the general population. People with MS who become depressed have a high rate of suicidal intent. There is also a high suicide rate in people with MS . . . The odds ratio . . . is twice what it is in the general population.” Dr. Feinstein “But the important point is depression is treatable,” said dr. feinstein. “And now we have the possibility that depression might be worsening cognitive difficulties as well.” Among the criteria for depression in The diagnostic and Statistical Manual of Mental disorders5, noted dr. feinstein, is a diminished ability to think or concentrate. “There is an understanding in the psychiatry population . . . that if you have a major depression, people who are depressed, express problems with their cognition, they feel they have cognitive impairment.” dr. feinstein highlighted research by dr. Peter Arnett’s team at Pennsylvania State university in State College, Pa. that found patients with MS who were depressed, compared to patients with MS who were not depressed, performed worse on various capacity demanding tasks and reading span tests (Neuropsychology 1999; 13:434–446, 546–556). One theory is that depression impairs cognitive and attentional capacity, then impairs working memory and then executive function. “There is another view, expressed recently by [dr.] Sarah Morrow’s research group,” said dr. feinstein. “They had a look at 349 people with MS, it was a retrospective study, they used a bootstrap analysis, and they showed that depression might in fact slow processing speed and then

on the basis of the slowed processing speed [patients] have difficulty with [their] memory and executive function. A slightly different theory for trying to account for why people with depression have cognitive problems.” The findings were published in the journal Neuropsychology (2016; 38:782–94). dr. Morrow is an associate professor of neurology at Western university in london, Ont. and THE CHRONIClE Of NEuROlOgY + PSYCHIATRY’s Neurology Editor. The severity of depression also impacts the degree of cognitive impairment, noted dr. feinstein (Cognitive Neuropsychiatry 2003; 8:161–171).

DEPRESSION IN MS IMPACTS COGNITIVE RESERVE dr. feinstein and his colleagues conducted research that examined cognitive reserve’s link with depression and cognition (Mult Scler feb. 2017; 1352458517692887). Cognitive reserve, he noted, is associated with protecting individuals from cognitive decline. Cognitive reserve is linked with premorbid IQ, the degree to which one participates in leisurely pursuits, and general intellectual enrichment prior to MS onset. In a cross-sectional study, a sample of 155 patients with MS and 115 healthy controls, he found that the MS group demonstrated greater decreases in leisure activity over time compared to the healthy controls. depression accounted for 17% of the variance in determining the level of leisure activity. “You will see a powerful example here about how depressed people with MS are not pursuing something in their life that might be protective from a cognitive point of view,” said dr. feinstein. dr. feinstein and his team also investigated the role of depression on distractibility in people with MS in a real-world setting. “[usually] when we bring someone in for cognitive testing we put up a sign that says ‘quiet please, testing in progress,’” he said. “But this is not a real world situation. We live in a busy environment, there is noise around us all the time.” In their study, published in MSJ: Experimental Translational Clinical (2016; 2:15), 102 people with MS completed a computerized Symbol digit Modalities Test. Half of the participants completed a test with added computer-generated distracters (i.e., a phone ringing, a car horn, people talking) and the other half completed the test without the distracters. “depression, not anxiety, further impeded processing speed in people with MS, particularly in the presence of distracters,” said dr. feinstein. “given that distracters are ubiquitous in the real world, these findings highlight the potential influence of depression on cognition in the workplace and in the home. “What happens if we treat depression, might it improve cognition? And the answer is we don’t know,” concluded dr. feinstein. He added, “No MS data, but results from people with traumatic brain injuries are encouraging.”

HOT TOPIC: GUT MICROBIOTA IN MS Canadian Helen Tremlett, Phd, a professor at the university of British Columbia, vancouver in the faculty of Medicine, division of Neurology and the Canada Research Chair in Neuroepidemiology and Multiple Sclerosis, presented two of her recent studies

GUT MICROBIOTA IN EARLY PEDIATRIC MULTIPLE SCLEROSIS: A CASE-CONTROL STUDY

Tremlett H, Fadrosh DW, Faruqi AA, Zhu F, Hart J, Roalstad S, Graves J, Lynch S, Waubant E; US Network of Pediatric MS Centers. ABSTRACT

BACKGROUND AND PURPOSE: Alterations in the gut microbial community composition may be influential in neurological disease. Microbial community profiles were compared between early onset pediatric multiple sclerosis (MS) and control children similar for age and sex.

METHODS: Children ≤18 years old within two years of MS onset or controls without autoimmune disorders attending a University of California, San Francisco, pediatric clinic were examined for fecal bacterial community composition and predicted function by 16S ribosomal RNA sequencing and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. Associations between subject characteristics and the microbiota, including beta diversity and taxa abundance, were identified using non-parametric tests, permutational multivariate analysis of variance and negative binomial regression.

RESULTS: Eighteen relapsing-remitting MS cases and 17 controls (mean age 13 years; range four to 18) were studied. Cases had a short disease duration (mean 11 months; range two to 24) and half were immunomodulatory drug (IMD) naïve. While overall gut bacterial beta diversity was not significantly related to MS status, IMD exposure was (Canberra, p<0.02). However, relative to controls, MS cases had a significant enrichment in relative abundance for members of the Desulfovibrionaceae (Bilophila, Desulfovibrio and Christensenellaceae) and depletion in Lachnospiraceae and Ruminococcaceae (all p and q<0.000005). Microbial genes predicted as enriched in MS versus controls included those involved in glutathione metabolism (Mann-Whitney, p=0.017), findings that were consistent regardless of IMD exposure.

CONCLUSIONS: In recent onset pediatric MS, perturbations in the gut microbiome composition were observed, in parallel with predicted enrichment of metabolic pathways associated with neurodegeneration. Findings were suggestive of a pro-inflammatory milieu.

regarding the gut microbiota in pediatric patients with MS during a “Hot Topics” session. “We found that children with and without MS had subtle differences in gut microbiota,” said dr. Tremlett, regarding her study published in the European Journal of Neurology (Aug. 2016; 23(8):1308– 1321) (see above abstract for more information). “It was suggestive of a pro-inflammatory milieu. And it did seem that there was an association with immunomodulatory drug exposure.” She said that future studies are warranted to better understand the direction of effect and —please turn to page 17

December 2017 n 11

Photo by Taxiarchos228, cropped and modified by Poke2001 (Paris-pano-wladyslaw.jpg) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

RIMS annual conference in Paris


sport

First Canadian guideline on concussion management in

Associate Editor, The Chronicle OR THE fIRST TIME,

a comprehensive Canadian guideline has been prepared to encompass the recognition, medical diagnosis, and management of suspected concussion sustained during a sporting activity. funded by the Public Health Agency of Canada and developed by the Expert Advisory Committee on Concussions within the national injury-prevention charity Parachute Canada, the guideline was created to be a nationwide standard of multi-disciplinary care from the moment of injury to safe return to sport. The committee is a group of 15 concussion experts from a range of fields including neurologists, neurosurgeons, physiotherapists, kinesiologists, other physicians and educators. “The true value of this guideline is to help all sports stakeholders to get on the same team to optiDr. Ellis mize the early recognition and standardized management of athletes with a suspected concussion,” said dr. Michael Ellis, co-chair of the committee, in an email interview with THE CHRONIClE Of NEuROlOgY + PSYCHIATRY. dr. Ellis is the medical

F

—Continued from page 3

REFERENCES

director of the Pan Am Concussion Program in Winnipeg and co-director of the Canada North Concussion Network. “In this way, whether it is a national team baseball player in Calgary or a Timbit hockey player in New Brunswick, all athletes with a

1. Parachute. Canadian guideline on Concussion in Sport. 2017. 2. Haring RS, Canner jK, Asemota AO, george BP, Selvarajah S, Haider AH, et al: Trends in incidence and severity of sports-related traumatic brain injury (TBI) in the emergency department, 2006–2011. Brain Inj 2015; 29(7–8):989– 992. 3. Barlow KM, Crawford S, Stevenson A, Sandhu SS, Belanger f, dewey d: Epidemiology of postconcussion syndrome in pediatric mild traumatic brain injury. Pediatrics 2010; 126(2):e374-e81. 4. Yeates KO, Taylor Hg.: Neurobehavioural outcomes of mild head injury in children and adolescents. Pediatr Rehabil 2005; 8(1):5–16. 5. Cassidy jd, Boyle E, Carroll lj: Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions. Archives of Physical Medicine and Rehabilitation 2014; 95(3 SuPPl):S278-S285. 6. Zemek R, Eady K, Moreau K, farion Kj, Solomon B, Weiser M, et al: Canadian pediatric emergency physician knowledge of concussion diagnosis and initial management. CJEM 2015; 17(2):115–122. 7. Stoller j, Carson jd, garel A, libfeld P, Snow Cl, law M, et al: do family physicians, emergency department physicians, and pediatricians give consistent sport-related concussion management advice? Can Fam Physician 2014; 60(6):548, 550–552. 12 n December 2017

suspected concussion are managed according to the same principles and a common protocol.”

SIGNIFICANCE OF SPORT CONCUSSION This push for a more uniform approach to concussion “is in keeping with the rising importance of concussions, symptomatic of the realization that concussions are brain injuries and that they are extremely common,” said committee co-chair dr. Charles Tator, project director of the Canadian Concussion Centre at the Krembil Neuroscience Centre, Toronto Western Hospital, and is a professor of neurosurgery at the university of Toronto. “[Concussions] are the most common of all brain injuries, and not everyone gets better from concussion,” said dr. Tator. “By that I mean you can die of concussion, and you can have lifelong disability from concussion. It is not just a ‘ding.’” He says that a major goal of the guideline is to have doctors giving consistent recommendations on graduated return to sport, return to school, and return to work. “We do not want one doctor to say ‘oh, go back to work right away,’ or ‘yes, you can go back to hockey immediately,’ and disregard the graduated return to play process that has been put in place.” Students going —please turn to page 13

8. Rotter T, Kinsman l, james E, Machotta A, Willis j, Snow P, et al: The effects of clinical pathways on professional practice, patient outcomes, length of stay, and hospital costs: Cochrane Systematic Review and Meta-Analysis. Evaluation & the Health Professions 2012; 35(1):3–27. 9. Reisner A, Burns Tg, Hall lB, jain S, Weselman BC, de grauw Tj, et al: Quality improvement in concussion care: influence of guideline-based education. The Journal of Pediatrics 2017; 184:26–31. 10. guyot A. Benefits of NICE accreditation for guidelines. Journal of Hospital Infection 2016; 92(1):5–6. 11. Carroll C: Qualitative evidence synthesis to improve implementation of clinical guidelines. Br Med J 2017; 356. 12. McCrory P, Meeuwisse W, dvorak j, Aubry M, Bailes j, Broglio S, et al: Consensus statement on concussion in sport-the 5th international conference on concussion in sport held in Berlin, October 2016. Br J Sports Med 2017; 51(11):838–847. 13. Meeuwisse WH, Schneider Kj, dvorak j, Omu OT, finch Cf, Hayden KA, et al: The Berlin 2016 process: a summary of methodology for the 5th International Consensus Conference on Concussion in Sport. Br J Sports Med 2017; 51(11):873–876. 14. Shewale AR, johnson jT, li C, Nelsen d, Martin BC: Net clinical benefits of guidelines and decision tool recommendations for oral anticoagulant use among patients with atrial fibrillation. Journal of Stroke and Cerebrovascular Diseases 2015; 24(12):2845–2853.

Ilgar Jafarov [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

by John Evans,


Sport concussion guideline useful for a wide range of medical professionals

—Continued from page 12

back to a learning environment too early after a concussion can be impacted by the noise, light, and high level of cognitive activity, dr. Tator said. Returning to sport too soon presents the risk of second-impact syndrome from subsequent concussions, which can be fatal. The guideline provides important direction for neurologists who are providing sideline or in-office care of acute concussion patients, said dr. Ellis. “As well as those neurologists who see concussion patients within the setting of multi-disciplinary concussion clinics.”

ACCESS TO CONCUSSION CARE Not all Canadians have access to a physician with expertise in concussion, noted dr. Tator, particularly in more remote communities. “We can put down on paper

that everyone should be seen by a medical doctor, and we can say that everyone should be cleared by a medical doctor for return [to sport, school, or work]. But is it adhered to?” Addressing the access issue is an ongoing project, dr. Tator said. One option, built into this guideline, is that if there is no physician available, assessment might be done by a nurse practitioner or nurse. Another system that could be implemented is the development of Dr. Tator novel telemedicine programs that allow patients in northern communities to connect remotely with specialized regional concussion clinics. A pilot project of telemedicinedelivered concussion care for pediatric patients living in northern Manitoba was recently launched by the Pan Am Concussion Program.

THE FUTURE OF THE GUIDELINE This guideline is only the first step of an ongoing process, said dr. Tator. The document published in july was intended to be relatively general, and apply to every sport, and also to many other concussion scenarios, such as children being injured at school. “The next stage of the process is to interact with the national sports organizations so that we can make the guidelines specific for sports in which concussions occur frequently,” dr. Tator said. The committee hopes to have sport-specific guidelines ready by spring 2018, he said. As well, the results of the next Berlin meeting, in 2020 will be considered and used to update the Canadian guideline. —Read the guideline, tools at goo.gl/UYN1xG

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ADAPTING THE 2016 BERLIN CONSENSUS To develop the guideline, the committee reviewed the consensus statement released by the fifth international conference on concussion in sport held in Berlin in Oct. 2016. The conference is held every four years. The Canadian guideline, “really took the principles from Berlin, from the world consensus, and made them more specific and applicable to our Canadian healthcare system,” said sports medicine physician dr. Shannon Bauman, medical director of Concussion North in Barrie, Ont., who was also on the Expert Advisory Committee. Because of the high workload Dr. Bauman of the family doctors who are often the first contact of a potentially concussed individual with the healthcare system, “one of the projects is to simplify the forms that are involved in concussion management,” said dr. Tator. “for example,” he said, “there is a list of more than 60 symptoms that you can have after concussion. Not everybody has the same symptoms, so there is nothing easy about the diagnosis of concussion or the management of concussion.” Because the committee acknowledge that a wide range of medical practitioners are involved in concussion management, they wanted as many people as possible to be knowledgeable about concussion, dr. Tator said. That includes psychiatrists, since a number of psychiatric conditions, including depression and anxiety, are common aspects of post-concussion syndrome, particularly after repetitive concussions, he said. To facilitate providing accurate, usable information on concussion to as wide a population as possible, there are a number of printable documents included with the guideline. These include: • A pre-season concussion education sheet, to help nonexperts at the site of sporting activity understand what a concussion is, and the common symptoms they should watch out for;

• A Medical Assessment letter to be completed by the physician or nurse practitioner who provides the initial medical assessment of the athlete; • A Medical Clearance letter in which the athlete’s physician can indicate what activities they are cleared to return to; • The Concussion Recognition Tool, 5th Edition (CRT5), to help non-professionals recognize and identify concussion symptoms in athletes when an injury occurs; • The Sport Concussion Assessment Tool, 5th Edition (SCAT5); and • The Child Sport Concussion Assessment Tool, 5th Edition (Child SCAT5), standardized tools for evaluating concussions, for use by physicians and other licensed healthcare professionals. The Medical Assessment letter contains information that the first medical professional to see the patient, such as an emergency room physician or a family medicine physician, will find useful in making initial decisions about guiding early concussion care and gradual progressions back to daily life, school/work, and physical activity, said dr. Bauman. When symptoms of a concussion persist beyond an expected duration or more complex neurologic signs or symptoms are present, a referral should be initiated to a neurologist or sports medicine physician, a neurosurgeon, pediatrician, physical medicine rehabilitation physician, or another physician role that has additional, specialized experience in concussion, she said.

December 2017 n 13


New tool for screening anxiety-related disorders in adults

n Screen for Adult Anxiety Related Disorder scale was adapted from child SCARED instrument

by Emily Innes-Leroux,

Managing Editor, The Chronicle

a screening tool for diagnostic and Statistical Manual of Mental disorders, 5th Edition (dSM-5) anxiety-related disorders including generalized anxiety, social anxiety, exasperation anxiety, and somatic/panic/agoraphobia in adults. The tool, called Screen for Adult Anxiety Related disorders (SCAAREd), is a 44-item scale that was adapted from the Screen for Child Anxiety Related Emotional disorders (SCAREd), which allows the adult scale to be used to follow children into adulthood. The psychometrics of SCAAREd were tested in a study published in the journal Psychiatry Research (july 2017; 253:84– 90). The researchers concluded that the SCAAREd “showed excellent psychometric properties supporting its use to screen adults for anxiety disorders, longitudinal studies following youth into adulthood, and studies comparing child and adult populations.” Canadian dr. Benjamin goldstein, department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, was involved with the international research. The study was led by dr. Melina Angulo from Mexico City. While there are structured interviews to diagnose anxiety disorders in adults such as Anxiety disorders Interview Schedule and the Structured Clinical Interview (SCId) for dSM-Iv, according to the investigators, those are time consuming and require extensive training to administer. NvESTIgATORS HAvE dEvElOPEd

I

ONLY TAKES FIVE TO SEVEN MINUTES The authors note that the scale is a time-efficient instrument that can be completed in approximately five to seven minutes. This makes it a promising tool in primary care and psychiatric settings. However, according to the investigator, participants with scores higher than the cut-off scores should be more extensively assessed to confirm the presence of anxiety disorders. “for clinicians involved in running anxiety disorder clinics, an issue is how to best screen patients referred? The screening that we usually do at our clinic in the Thompson Anxiety disorders Centre at Sunnybrook Hospital in Toronto involves a fairly laboursome telephone interview,” Neil Rector, Phd, senior scientist and director of research, department of Psychiatry, Thompson Anxiety disorders Centre, told THE CHRONIClE Of NEuROlOgY + PSYCHIATRY. dr. Rector was not involved Dr. Rector in the study. He added that he routinely uses the SCId to obtain anxiety diagnoses. “If we could replace that with a reliable self-report measure that would be incredibly helpful,” said dr. Rector, who is also a professor in the department of Psychiatry at the university of Toronto. dr. Rector pointed out that not all the dSM-5 anxiety disorders are included in this new scale. Also, that the previous dSM-4 classified anxiety disorders—obsessive compulsive

14 n December 2017

disorder and post-traumatic stress disorder—are not screened for in SCAAREd, but that they are often comorbid with the broader anxiety disorders. “[The scale is] an incredible first step, but we probably need to broaden it out so that we have a screen that could be done at one point of time that could map out the overlapping comorbidities in the broader mood and anxiety spectrum that we so often see,” said dr. Rector. “do we hand out this scale for the four diagnoses that it is tapping into [and] do we hand out another screening measure for depression and bipolar conditions and do we hand out another measure for OCd and PTSd?” he said.

POTENTIALLY NEED FOLLOW-UP INTERVIEW dr. Rector believes that the tool would need to be followed-up with a clinical interview to better understand a patient’s possible comorbidities and to determine where to start treatment and treatment targets. “I think this would be potentially useful for screening at the primary care level,” said dr. Rector, adding that it can be used as a way to determine if a patient should be referred to a psychiatric setting for further screening. The investigators noted that a limitation of the study was that very few participants had anxiety without depression, which precluded the use of the SCAAREd to compare participants with “pure” anxiety and “pure” depression. Another limitation, according to the authors, was that there were no focus groups or studies done to determine the understandability of the questions. They state, however, that research assistants and other investigators read the scale for understandability and items were rewritten accordingly and that in all studies no understandability problem has been identified. “I think the sentences are very clear and meet psychometric conditions for item creation that these are clear items testing single constructs,” said dr. Rector.

LANGUAGE ADAPTED FOR ADULTS The SCAREd was modified for language and/or situations appropriate for adults. for example: “I get headaches when I am at school” was modified to “I get headaches when I am at school, at work or in public places.” As well, four gAd items that are part of the dSM-5 criteria for adulthood were added and one item from the child scale was eliminated: “I follow my mother or father wherever they go.” A further limitation, noted the investigators, was that all participants with agoraphobia included in this study also had panic disorder; consequently the symptoms of agoraphobia and panic disorder are grouped together as one factor. “That problem also reflects a long difficulty in understanding how these two conditions overlap. “We have historically had panic disorder with and without agoraphobia and as we move to the dSM-5 we have seen the separation of panic disorder and agoraphobia,” said dr. Rector, noting that this factor of the scale probably needs more work. —Read more information at goo.gl/RNQhz1


High-persistent SEPAD in children leads to mental problems in pre-adolescence

—Continued from page 1

dr. Battaglia and colleagues used multi-informant (children, teachers, family), multi-point (age eight, 10, 12, 13 years) assessments of 1,290 children in the Quebec longitudinal Study of Child development who had been categorized between age 1.5 and six years into four specific separation anxiety trajectories: low-persistent, low-increasing, highdecreasing, and high-increasing. The participants in the highincreasing trajectory were compared to participants in the other three traDr. Battaglia jectories for a child’s internalizing (anxiety and depression symptoms) and externalizing behaviours (hyperactivity, physical aggression, opposition, and behaviour disorder), physical health, academic achievement, and maternal anxiety. The investigators found that the high-increasing separation anxiety trajectory showed consistently more internalizing symptoms compared to the members of the other three trajectories. They did not observe differences across the four trajectories with regard to externalizing behaviours. Participants in the high-increasing trajectory achieved generally less academically than the children in the three other trajectory groups as reported by the participants’ teachers answering the question “relative to his/her classmates, how would you rate this child’s current overall academic achievement?” on a five-point rating scale. The investigators observed that the high-increasing group were generally more prone to physical illnesses and significant differences were observed for asthma at age 10 and 13 years and for headaches at age 12 years. The authors noted that previous research has found higher than expected asthma and respiratory conditions in childhood SEPAd and that it has been epitomized by a CO2 hypersensitivity in these children.

NEED TO FURTHER EXPLORE PAIN “I would like to think that this [research] may promote a deeper reflection, maybe including a conversation about pain,” said dr. Battaglia, associate professor of psychiatry at the university of Toronto. He said that often it is perceived that children with SEPAd who say they have a “belly-ache,” or another ache symptom, are lying/overemphasizing as a strategy to be able to stay at home and to elicit their parents’ attention. “But, what if these kids are actually feeling real pain . . . that minimal stimuli, that otherwise in other kids would not be painful, for them [is] truly painful,” said dr. Battaglia. “We tend to think typically . . . that anxiety and depression and pain go together in one-directional causal chain. The classical medical model, of course, [is that if] someone has . . . chronic pain you get anxious and you get depressed—so A causes B,” said dr. Battaglia.

“But, what if these things start together first, early in life second, and third, not because one causes the other, but because they share some determinants— maybe genetic, maybe environmental—that simultaneously act in such a manner that a kid becomes more liable to become anxious and his/[her] nociception is altered,” he said.

SIMILAR FINDINGS OBSERVED IN ANIMAL MODELS dr. Battaglia said that he has observed altered nociception in animal models of mice who show separation anxiety symptoms. “In a . . . parallel way, I am running animal models of early separation and of course these mice are more anxious about separation, but they have lots of other interesting [comorbidities],” he said (PloS One 2011; 6(4):e1863) (Sci Rep 2016; 6:25131). “[The mice] are more sensitive with their respiration system, their respiration physiology is more reactive to light suffocative stimuli so they hyperventilate more easily than mice who have not been separated. And they are more sensitive to painful stimuli. And what we are seeing that at the base of these physiological re-arrangements are different expressions of genes, most likely brought ‘on-line’ by our interfering with early maternal environment.” While the animal model findings are not yet ready to be applied to humans, dr. Battaglia noted that the observations in this longitudinal child cohort were fairly consistent with his hypothesis from the mice studies. In the longitudinal study, dr. Battaglia and his

team also found that mothers of children with highincreasing SEPAd self-rated themselves as significantly and consistently more anxious than mothers of children from the other trajectories. This is a finding that has been observed in his previous studies and other investigators’ work, according to dr. Battaglia (Arch Gen Psychiatry jan. 2009; 66(1):64-71) (Biol Psychiatry june 2010; 67(12):1171–11177) (Depress Anxiety Apr. 2012; 29(4):320–327). “familial-genetic continuity between childhood SA/SEPAd and adult Pd-AgO is thus supported by our longitudinal population-based family study,” noted the researchers in the discussion section of their study. dr. Battaglia said that this finding points to potential environmental and genetic factors that are impacting both the mother with Pd-AgO and the child with SEPAd. “[We] are looking at parallel stories.” dr. Battaglia said that knowing there is a large young population with pain related to anxiety, leads to an important question for clinicians to consider: “How can we best address this?” One way, according to dr. Battaglia, is to be “protective and fore-seeing toward other risks in later adolescence, early adulthood and among these risks at this point I would definitely add opioid [addiction], because opioids are prescribed too easily.” “use this information in a more stringent way and think prospectively about how this boy or girl will present in four, five, or six years from now,” he added.

December 2017 n 15


Surveying the current

Neurology literature Migraine, prolonged aural fullness may share etiological factors

Telehealth home exercise program may raise PD patient adherence to physiotherapy

Study confirms higher rate of epilepsy among individuals with systemic lupus erythematosus

16 n December 2017

T

Recently come across something from the peer-review literature that you consider to be interesting or impactful? Share it with your colleagues. E-mail your clippings, along with your comments, to: health@chronicle.org

between migraine and prolonged aural fullness, according to findings published online ahead of print in Otolaryngology—Head and Neck Surgery (Nov. 1, 2017). HERE MAY BE AN ETIOlOgICAl ASSOCIATION

The investigators present a case series of isolated, prolonged aural fullness (Af) and its relation with migraine. A group of 11 patients (mean age, 52 years) were included. All were experiencing isolated, persistent Af for six months or more, where all possible etiologies were ruled out. The patients were prescribed migraine dietary and lifestyle changes, and medical migraine prophylactic therapy. Of the 11 patients, six (54%) met International Headache Society criteria for migraine with or without aura. Researchers found that there were statistically significant improvements in the perceived sensation of Af, as measured using a visual analog scale and quality of life questionnaires (p<0.001, 95% confidence interval [CI], 4.7 to 6.72, and p<0.001, 95% CI, -5.3 to -2.7, respectively. This improvement in Af experience after instituting migraine lifestyle changes and prophylaxis suggests an etiological association between migraine and prolonged aural fullness, the authors concluded. —More information at goo.gl/n8zoBs

home exercise program physical therapy for patients with Parkinson’s disease (Pd) appears to be a feasible physical therapy solution, as it may increase long-term exercise adherence and thereby improve health outcomes. These findings come from a case report published online ahead of print in Journal of Neurologic Physical Therapy (dec. 1, 2017).

A

TElEHEAlTH SYSTEM AIMEd AT IMPROvINg

The telehealth system, System for Technology-Augmented Rehabilitation and Training (START), was incorporated into an established Pd physiotherapy protocol, the lee Silverman voice Technique BIg (lSvT BIg). In the first four weeks of a fourmonth intervention, a physical therapist guided the participant—a 67-year-old woman with Pd at Hehn and Yahr Stage II— through the lSvT BIg protocol. START was introduced at week three, and the participant was encouraged to complement her daily home exercise program with START through the end of the fourth month. Improvements in gait, endurance, balance confidence, and quality of life were seen from the start of the assessment through the end of month one, and all outcomes were maintained or improved by month four. Monitored through the START system, the participant’s adherence to the twice-daily home exercise program prescription was 24%, with overall daily participation at 78%. She reported an overall high satisfaction with START, though the autonomous feedback from START was a limiting concern. No technical issues or adverse events were reported. A video talk on the case from the authors is available here: goo.gl/6kM2wd. —Find more information at https://goo.gl/vX4Z8W

(SlE) has confirmed a higher prevalence of epilepsy in this population, and physicians should have a lower threshold for suspecting epileptic seizures in these patients, researchers report online ahead of print in Neuroepidemiology (dec. 1, 2017).

A

lARgE STudY Of INdIvIduAlS WITH SYSTEMIC luPuS ERYTHEMATOSuS

The authors note that while an increased risk of seizures has been described in several inflammatory/autoimmune disorders in extant literature, so far, relatively few and small sized studies have been conducted. To address this, they aimed to investigate the link between seizure and SlE utilizing a large sample of subjects and extensive data analysis. This study included 5,018 patients with SlE and 25,090 age- and gender-frequency-matched controls, using data from the medical database of Clalit Health Services in Israel. Chi-square and t tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. Investigators found the proportion of epilepsy was significantly higher among individuals with SlE (4.03% vs. 0.87%, p<0.001). logistic regression and adjusting for confounding factors revealed that older age (70 years or older) was a negative predictor of epilepsy (odds ratio [OR]) 0.42 (95% confidence interval [CI] 0.27-0.62], p<0.001), while presence of SlE was a positive predictor (OR 4.70 [95% CI 3.94-5.82], p<0.001). Interaction between SlE and higher age resulted in high OR of 5.47 for epilepsy (95% CI 2.53-11.9). —Read more at goo.gl/XwL63b


Magnetic seizure therapy: A potential option for patients with severe depression

—Continued from page 7

repetitive transcranial magnetic stimulation (rTMS), which can be offered when patients do not respond to pharmacologic therapy.

rTMS AN OPTION FOR PATIENTS WHO ARE PHARMACOLOGIC NON-RESPONDERS “If you have not gotten better on at least two medication trials, then the odds start to favour doing rTMS more than further medication trials,” said dr. jonathan downar, co-director of the MRI-guided rTMS Clinic at university Health Network in Toronto and scientist at the Toronto Western Research Institute. “It’s considered safe and tolerable, and about one out of every three patients achieves remission.” Another one-third of patients who undergo rTMS experience some improvement and the other Dr. Downar one-third do not improve with rTMS, noted dr. downar. Investigators are researching the utility of functional magnetic resonance imaging (fMRI) to detect neurological biomarkers to distinguish responders from non-responders (Nature Medicine 2017;

23:28-38). The disadvantage of the treatment is that patients need to accommodate several weeks of daily visits to a healthcare facility in their schedules to access the treatment, according to dr. downar. There is a recommendation to fund rTMS treatment in the province of Ontario, but that recommendation has not yet been implemented, said dr. downar. Clinics for rTMS are available in Ontario, Quebec, Saskatchewan, and are starting to be available in British Columbia and Alberta. Patients who discontinue rTMS usually cite that they are opting to do so because of the pain associated with the treatment, which patients can rate as high as six out of 10 on a likert scale, said dr. downar. Another non-pharmacologic treatment for depression is magnetic seizure therapy (MST), which is only offered in Canada at the Centre for Addiction and Mental Health (CAMH) in Toronto.

MAGNETIC SEIZURE THERAPY AT CAMH MST works similarly to electroconvulsive therapy (ECT), but unlike ECT, MST is memory-sparing, according to dr. Z. jeff daskalakis, chief of Mood and Anxiety division, and co-director of the Temerty

Centre for Therapeutic Brain Intervention at the Campbell family Mental Health Research Institute at CAMH. “MST is used to produce a seizure,” said dr. daskalakis, describing the therapy as investigational and noting that it requires administration of a general anesthetic. “It works about 50 per cent of the time in patients who do not otherwise respond to medication treatments.” Patients with severe disease are candidates for MST, but patients who have a history of seizures or Dr. Daskalakis epilepsy or other neurological conditions would not be potential candidates for MST, noted dr. daskalakis, also professor of psychiatry at the university of Toronto. The protocol for MST is three treatments per week for a period of up to two months for initial therapy. After which, MST may be administered on an ongoing basis as a maintenance treatment. Non-proprietary and brand names of therapies: sertraline (Zoloft, Pfizer Canada Inc.); fluoxetine (Prozac, Eli Lilly Canada Inc.)

Maintaining ‘ideal’ cardiovascular health could reduce Alzheimer’s disease risk

—Continued from page 9

fiable risk factors (diabetes, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity) could potentially prevent as many as 1.1 to three million Ad cases worldwide (The Lancet Neurol Sept. 2011; 10(9):819–828). “But does this work?” asked dr. deCarli. “Well [dr.] donald lloyd-jones came up with this idea of ‘life’s Simple 7’ and it is in the context of the American Heart Association’ (AHA) Strategic [Planning Task force and Statistics Committee] . . . to define and set national goals for cardiovascular health.” LIFE’S SIMPLE 7: • manage blood pressure, • control cholesterol, • reduce blood sugar, • get active, • eat better, and • stop smoking.

The life’s Simple 7 diet focuses on a model called “dietary Approaches to Stop Hypertension” (dASH): • fruits and vegetables: ≥4.5 cups per day • fish: ≥two 3.5-oz servings per week • fiber-rich whole grains: ≥three 1-oz servings per day • Sodium: <1,500 mg per day • Sugar-sweetened beverages: ≤ 450 kcal (36 oz) per week

LIFE’S SIMPLE 7 AND COGNITION Investigators have studied the association between cardiovascular health (using life’s Simple 7) and cognitive impairment, noted dr. deCarli (J Am Heart Assoc june 2014; 3(3)). The researchers used the REasons for geographic And Racial differences in Stroke (REgARdS) participants aged 45+ years who had normal global cognitive status at baseline and no history of stroke (n=17,761) and calculated baseline life’s Simple 7 scores (range, 0 to 14) for the participants. They then identified incident cognitive impairment using a three‐test measure of verbal learning, memory, and fluency. They reported that compared with low cardiovascular health levels, intermediate and high cardiovascular health levels were both associated with substantially lower incidence of cognitive impairment. dr. deCarli and colleagues, using the framingham data, studied the association

of ideal cardiovascular health (as measured with a seven-point scale using the life’s Simple 7 criteria) with vascular brain injury and incident dementia. The investigators of the study published in Stroke (May 2016; 47(5):1201– 1206) found that cardiovascular health is inversely associated with stroke, vascular dementia, frontal brain atrophy, and cognitive decline on tasks measuring visual memory and reasoning. The authors concluded that their data suggests that “adhering to CvH [cardiovascular health] guidelines protects against all forms of vascular brain injury, lessening the burden of cognitive decline, stroke, brain atrophy, and dementia, including Ad. “It looks like the longer you have the ideal [cardiovascular health], the longer you maintain life’s Simple 7, the better you are going to do with the brain structure and your cognition,” said dr. deCarli.

Gut microbiota and pediatric MS

—Continued from page 11

the confounders. dr. Tremlett and colleagues also conducted a study to determine if there is an association between the gut microbiota and relapse risk in pediatric patients with MS. “Interestingly we still don’t know what triggers or facilitates an MS relapse,” said dr. Tremlett. “But, I think there is general agreement that the immune system is involved and the gut microbiota is a major modulator of the immune system. dr. Tremlett and her colleagues explored the association between baseline gut microbiota in 17 relapsing-remitting pediatric MS cases and risk of relapse over a mean 19.8 months follow-up. After covariate adjustments for age and immunomodulatory drug exposure absence of fusobacteria was associated with relapse risk (hazard ratio=3.2 (95% CI: Dr. Tremlett 1.2–9.0), p=0.024). “It is interesting that the findings suggest that gut microbiota was associated with relapse risk,” said dr. Tremlett. “Specifically, depletion of fusobacteria was associated with more than three times the hazard of an earlier relapse. I think further investigation is warranted.” December 2017 n 17


“Feelings of love and gratitude arise directly and

spontaneously in the baby in response to the love and care of his mother.”

—Melanie Reizes Klein, Austrian-British psychoanalyst (1882–1960)

amilton-based psychiatrist Dr. Karen Saperson was the 2017 recipient of The Royal College of Physicians and Surgeons of Canada’s Associated Medical Services (AMS)/Donald R. Wilson Award. Dr. Wilson (1917–2017) was past president of AMS Inc. (1983–1996) and led the initiative known as Educating Future Physicians of Ontario (E.F.P.O.) that was based on making undergraduate medical education in Ontario more responsive to the changing needs of society. The award is presented annually to a medical Founder educator or an identified leader who has demonstrated excellence in integrating the CanMEDS roles into a Royal College or other health related training program. Dr. Saperson is a professor of psychiatry and associate chair, Education, in the Department of Psychiatry and Behavioural Neursociences at McMaster University. She is the past program director of both the Psychiatry and Geriatric Psychiatry residency programs and academic head of the Division of Geriatric Psychiatry at McMaster. She is also a staff psychiatrist at St. Joseph’s Healthcare. THE CHRONIClE’s Emily Innes-Leroux spoke with Dr. Saperson about this award and her work in education and geriatric psychiatry.

H

Dr. Karen Saperson

What did it mean to you to be awarded the AMS/Donald R. Wilson Award? It is probably one of the most significant honours in my professional life, for many reasons. To be recognized in this way and in the name of donald Wilson, who is such an iconic figure and who did so much for the field, and also to have the AMS as a partner in terms of their emphasis on compassion in medicine, it means a huge amount . . . This experience has made me aware that there are many excellent educators out there who are not necessarily acknowledged or recognized by awards. I am here from the generosity of my colleagues who took the trouble to nominate me. And I think that is perhaps something that we should all be more mindful of supporting each other, recognizing each other and taking the trouble to do that, the way my colleagues have done for me.

Why do you think mentorship programs are so important? . . . I think [young physicians] are having to balance knowledge of medicine in the context of sociopolitical factors, economic factors, [and so] it is not simply a matter of going and seeing your patients and doing the best you can in providing evidence-based care. [There are also] the stresses of life, trying to find that balance between profes18 n December 2017

status: Geriatric Psychiatry subspecialty

sional life and family life. The expectations and accountabilities for young physicians have grown significantly. There is pressure to publish and there are pressures to present and disseminate knowledge, to be fiscally responsible and ethically sound, and all kinds of things above and beyond doing their best and seeing their patients. I think that having some mentorship, guidance, and support for when things are not going well, and guiding young colleagues to focus their time and energy, because there is only so much energy to go around, is very important.

How did you get involved in creating a program specifically for female mentorship? I see my role as a senior member of the department to really facilitate other faculty members’ creative ideas and to help them to reach their ability to innovate. The idea for the writing mentorship [came from] another faculty member in my department, dr. Ana Hategan, so my role really was to assist and guide her, and help to promote her ideas. We looked at the literature and there is a clear gender difference, even though in medicine more than 50% of medical students . . . are women, in terms of the numbers of publications [by women] there is a significant gender discrepancy. And the reasons for that might be many. Taking leave to raise a family may be one reason, but it is probably not the only reason. dr. Hategan deliberately started to really encourage female residents [and medical students] working with her to write up the cases that they were seeing in practice together and I helped to facilitate and promote that, but I certainly don’t want to take credit for [the program]. To help encourage it, to help others to join in . . . I think that is really my role.

What did it mean to you to receive Founder status for

the subspecialty of Geriatric Psychiatry? I am only one of many working in the new subspecialty of geriatric psychiatry to receive this recognition. True credit goes to many respected senior colleagues who pioneered, championed, and advocated for us to have a newly recognized subspecialty in 2012/2013. Before that we were ‘psychiatrists with an interest in geriatric psychiatry’ and now we are a sub-specialist, in keeping with the united States and other parts of the world. It is a huge honour to be recognized in that way as having been part, just a small part, of the group that was pioneering a brand new subspecialty.

What do you think is current novel research in the area of geriatric psychiatry? An area of intense study is the prevention of cognitive impairment. I think we are much more aware of things to do that help us to age in a healthy way, looking at things like diet, exercise, and engaging socially with others. The questions [is] can these things help delay the onset of dementia, which, of course, is one of the most significant societal concerns given the aging demographic. And I think there is some emerging data to say that if you look after your vascular health, your blood pressure, diabetes, weight, and diet, that we can slow the rates of cognitive decline. Not completely reverse the process or completely prevent it, but perhaps change the numbers.

What is new in the area of medical education? Currently, much emphasis is being placed on the Royal College’s Competence By design or CBd framework that is being applied to all residency programs across Canada in a timed rolling out. Psychiatry will ‘go-live’ in 2019 and psychiatry subspecialties including geriatric psychiatry in 2020. This initiative will have significant implications for residents and faculty. One of my areas of interest in education research is: What makes an excellent faculty supervisor? We know that residents are flexible and will be ready to embark on training in the new methodology, but how are we going to train the faculty who have been doing things in the same way for decades to embrace this same model, this new approach? A group of my colleagues and I are trying to define the qualities of an excellent supervisor and see what we can learn from that to be useful in training new faculty. One of the early findings that we [have learned] is that the quality of the relationship between the learner and the supervisor [does] matter in order for learning to be effective. —Who’s making a difference near you? Tell The Chronicle, so we can tell our readers. Write us at health@chronicle.org


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The Chronicle of Neurology & Psychiatry December 2017  
The Chronicle of Neurology & Psychiatry December 2017  
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