Evidence of meeting #115 for Veterans Affairs in the 42nd Parliament, 1st session. (The original version is on Parliament’s site, as are the minutes.) The winning word was symptoms.
A recording is available from Parliament.
Liberal
The Chair Liberal Neil Ellis
Good afternoon, everybody. I now call the meeting to order.
Pursuant to Standing Order 108(2), a study of the effects of mefloquine use among Canadian veterans, today we have two witnesses appearing as individuals: Dr. Jonathan Douglas, a psychologist with Central Ontario Psychology; and Dr. Penelope Suter, an optometrist. She is on a video conference from Bakersfield, California.
Dr. Suter, welcome. We'll start with your opening statement.
Dr. Penelope Suter Optometrist, As an Individual
Thank you and good afternoon.
I'm a private practice optometrist with a specialty in neuro-optometry. I received my doctoral degree from the University of California at Berkeley.
My interest in the brain and vision began early in my career. After receiving my optometry degree, I spent 22 years doing part-time visually evoked potential research, measuring brain responses to visual stimuli, as co-director of the vision laboratory at the California State University in Bakersfield.
In my private practice I have been practising, writing and lecturing in the field of neuro-optometry for nearly 25 years. My co-editor Dr. Lisa Harvey and I published what is considered the most comprehensive text reference book to date on vision rehabilitation following brain injury. We worked hard to include both the basic science and clinical science involved in visual dysfunction and visual rehabilitation following brain injury.
Neuro-optometrists are interested in testing and treating visual function, including eye movements, eye coordination, visual perception of objects and visual perception of space and motion, as well as how we integrate those visual percepts with the other senses and the motor system so that we can move through space and act on objects. Visual processing is so distributed throughout the brain that it is difficult to injure the brain without some visual consequence.
I am here today not as an expert in mefloquine toxicity and the visual system, although I am happy to share what I know on the subject. I'm not sure that we have experts on the visual system and mefloquine toxicity at this point. However, I am here as a neuro-optometrist who has diagnosed hundreds of patients who have subtle vision deficits resulting from acquired brain stem injury that can mimic or exacerbate the symptoms of post-traumatic stress disorder—PTSD—or other psychological diagnoses.
Quinolones have been shown to cause brain stem lesions. I am here because just like the patients I see with subtle vision dysfunction resulting from other acquired brain stem injury, patients with mefloquine toxicity are at risk of being diagnosed with PTSD or other stress- or anxiety-related disorders when they actually suffer from neurologic vision deficits. I am here to tell you that every patient who suffers mefloquine toxicity and has PTSD-like symptoms, or difficulty reading, or photophobia, or difficulty with balance or dizziness, or feelings of disorientation or anxiety, needs a neuro-optometric workup. Neuro-optometrists and neuro-otologists can test for biological markers of brain injury that other professionals simply do not.
Ordinarily, our visual system and our vestibular system work together to create the perception of a stable physical world around us so that we can move through it with confidence. However, imagine suddenly living in a physical environment that moves and shifts just a little as you move your eyes—not enough for you to be able to say, “Oh, the floor just dropped three inches when I looked to the right”, but just enough to make you feel a little uneasy or queasy, or startled or disoriented, or where the space around you shifts, expanding on one side and contracting on the other.
When you walk toward an object that is straight ahead of you, you find that you're always veering to one side because your visual perception of straight ahead has been shifted from the reality of the physical straight ahead. All of these visual symptoms are common following acquired brain stem injury. They cause difficulty with balance and feelings of disorientation and anxiety because the physical world that we depend on to stay stable under our feet, in our hands and in our visual perception is no longer reliable.
If you have a visual problem that destabilizes the perception of the physical world around you, as I have described, the vestibular system will attempt to keep you upright. If you look to the right side and your visual system says, “Oh, something shifted,” and you get startled, your vestibular system will say, “It's okay. I know where upright is. I know where gravity is,” and it will rescue you. If you have a vestibular problem, the visual system can help stabilize you.
Some of you may remember having drunk enough alcohol to have closed your eyes and have the world start spinning, and then you opened your eyes to make it stop. That is your visual system rescuing you from your vestibular system. If, however, you have both a vestibular and a destabilizing visual deficit, then you suddenly live in an amusement park funhouse.
I want you to think for just a moment, if you were to wake up in a world that was that distorted, how you would try to explain that to your doctor to get help. What words would you use? What would you say? You don't have that spinning dizziness that you get with severe vestibular vertigo. Do you think that once you tried to explain it to them you would be sent to a neuro-optometrist to diagnose your subtle visual deficits creating this instability or exacerbating this instability, or do you think you would be sent to counselling, psychology or psychiatry?
Most of you have probably never heard of neuro-optometry before these meetings, and the same is true for your physicians. This is a common problem for many patients with mild acquired brain injury who can go for years or for a lifetime without ever getting diagnosed. It is certainly possible to have PTSD concurrently with subtle brain stem injury-related visual and/or vestibular deficits, but the treatment is very different for these diagnoses, and patients with mefloquine toxicity deserve accurate diagnosis and treatment with neuro-optometry and neuro-otology.
That's really what I wanted to come talk to you about today. Thank you for the opportunity.
Dr. Jonathan Douglas Psychologist, Central Ontario Psychology, As an Individual
Thank you for giving me this opportunity today. It’s quite humbling, as I do not consider myself an expert in quinism. Instead, I’m an expert in operational stress injuries, or OSIs—diagnoses that arise from the stress of military training and operations, including PTSD, depression, and adjustment reactions, and any of the myriad other problems that arise as a result of being thrust into extremely demanding situations.
I’m very pleased that the committee will be hearing from the real experts on quinism. In particular, I have learned much from Dr. Remington Nevin, who has studied quinism extensively and will be able to teach you much more than I can about the neurological damage that it causes.
I’m here today primarily because I have listened to veterans. Through doing so, I have learned about the challenges associated with mefloquine, including the difficulty that diagnosing it can represent.
I have worked with veterans for about 15 years now, and as part of my work I have completed many psychological disability assessments. For most of these, the issues associated with quinism have simply not been on my radar. It’s not something there’s much awareness of in my field.
To diagnose an operational stress injury, I begin with a clinical interview. I need to understand the veteran’s presenting symptoms, and I gather a history so that I can understand how the veteran was functioning before and after exposure to the military. I look at the operational history of the veterans, including what tours they went on and the traumatic events that occurred. We look at physical injuries, including exposure to blasts, as well as any other physical issues that might arise from the rigours of training and deployment. I review what documentation I have available, which is often pretty scant, and I administer psychological tests. From these, I’m able to identify the veteran’s symptoms, and in combination with the history, I can draw conclusions about the diagnosis and its probable link to military service.
I’d like to take a moment to review the diagnostic criteria for PTSD. You may already be reasonably familiar with these, but please bear with me, as I think it’s worth reviewing them in this context. The diagnosis of PTSD is distinctive among psychiatric diagnoses. That’s because diagnosis begins not with the symptoms presented by the patient but with an examination of an event.
Criterion A is directly experiencing or witnessing actual or threatened death, serious injury or violence. In the course of their careers, many, if not most, veterans will experience an event that meets criterion A; however, they don’t all end up with PTSD. They must experience the following symptoms, which arise following the event.
Criterion B requires one intrusion symptom from among the following: intrusive memories of the event, recurring dreams in which the content or mood of the dream can reflect the trauma, dissociative reactions such as flashbacks in which the person feels or acts as if the event is happening again, intense or prolonged psychological distress at exposure to reminders of the event, or physiological reactions to reminders of the event.
Criterion C requires one avoidance symptom—either efforts to avoid distressing memories, thoughts or feelings associated with the event, or efforts to avoid external reminders of the event, such as people, places, conversations, activities or situations.
Criterion D references two symptoms of negative alteration in cognition or mood, including the inability to remember some aspects of the event; exaggerated negative beliefs about oneself, others or the world, such as, “I'm broken, I'll never get better” or “No one can be trusted”; distorted beliefs about the cause of the event, leading to blame of self or others; a persistent negative emotional state such as fear, anger, guilt or shame; withdrawal from activities; feeling detached or estranged from others; and the inability to experience positive emotions.
Criterion E references two symptoms of alteration in arousal and reactivity, including irritability or angry outbursts, reckless or self-destructive behaviour, hyperviligance, an exaggerated startle response, problems with concentration and sleep disturbance.
Criteria B through E represent the symptoms of PTSD, and in each case, there should be evidence that the symptom began, or at least worsened, following the trauma. In these symptoms, you'll find the echoes of other OSIs, including depression or anxiety disorders. Substance abuse can be used to self-medicate and mask many of these symptoms. Those who have strong reactions to events that don't meet criterion A might be diagnosed as having an adjustment disorder. All of these are common OSIs.
For our purposes, there is one more important criterion for PTSD. Criterion H says that these symptoms must not be attributable to the physiological effects of a substance such as mefloquine.
That final criterion is pretty much universal in DSM-5. It is found among the diagnostic criteria for most disorders. It's so common that it's actually easily overlooked. When you're dealing with psychological trauma, it's rare to see someone in clinical practice whose symptoms can be attributable solely to the effects of a substance. In fact, before I had heard of mefloquine I was not aware of any substance that could mimic PTSD.
This substance was often prescribed in proximity to a traumatic event. When we look at the symptoms of quinism, we're going to see that they mimic many of the symptoms of PTSD and other OSIs.
According to the work of Dr. Nevin, the adverse effects of mefloquine can include the following psychiatric symptoms: anxiety; depression; panic attacks; severe mood swings; agitation; aggression; restlessness; mania, such as racing thoughts, irritability, paranoia or excessive goal-driven behaviour or euphoria; psychosis, including paranoia, delusions and hallucinations; dissociative symptoms, such as derealization and depersonalization; or sleep disturbance, including terrifying, intense nightmares or sleep paralysis, an experience like being awake in a body that will not move, often accompanied with a terrifying hallucination.
With varying degrees of frequency, all of these symptoms can and do present as sequelae to exposure to psychological trauma. They also represent the prodromal presentation of mefloquine, those symptoms that may appear with initial toxicity or as a side effect, an adverse reaction to the drug. They may also persist beyond the application of the drug, in some cases for years.
I am thinking of two veterans I have worked with. Both meet criterion A for PTSD and both present with an unusual feature that I rarely see in OSIs: hallucinations. Only one was exposed to mefloquine, and he experienced the full prodromal reaction—nights of severe terror punctuated with what seemed to be auditory hallucinations of animals screaming in the forest around him. Today he suffers from tinnitus and a persistent auditory hallucination consisting of mumbling voices, along with other more typical symptoms such as irritability, anxiety and mood disturbance.
It was years after his initial diagnosis of PTSD that the issue of mefloquine came up, and that was the first time I had ever heard of the word. I only heard about it because he brought it to my attention. As we've seen, PTSD should not be diagnosed when the symptoms can be explained by the impact of a substance such as mefloquine. Does this mean that his diagnosis is not accurate? Frankly, it's possible, but I think the question may be more complex than a simple yes or no answer.
One of the challenges in clarifying the diagnostic conundrum is that veterans may not always be able to accurately reconstruct the order in which events occurred, particularly such vague events as the emergence of a psychological symptom.
Let's consider a possible timeline. A soldier is deployed overseas on his first tour of duty. There are no prior exposures to traumas. To prevent the malaria, the soldier receives a course of mefloquine. He and his buddies joke about how rough their Friday nights are after they receive their weekly dose of the drug, but they're either not aware of the risks of continuing to take it or they dutifully push through. Almost immediately after treatment, the soldier is exposed to a war zone, with all the horrors that entails. When the subsequent symptoms arise and persist, are they solely due to the mefloquine or are they solely due to the exposure to the trauma?
Soldiers are not always the greatest historians. After years of pushing their emotions to the side and ignoring discomfort, it can be difficult for them to remember precisely when a symptom arose. In the midst of a war zone it's only natural to be anxious, vigilant and irritable. Years may pass before the psychological injury is assessed. How are we to say whether the symptoms are due to quinism or to trauma?
There are some symptoms more neurological in nature that might be helpful, things such as difficulty with balance, vision, vertigo or tinnitus, which do not typically present solely as the result of PTSD. Again, though, these have their own confounding variables, including the impact of blast injuries and concussions.
Of course, if the mefloquine was not taken on the first tour, but after the soldier was already exposed to chronic trauma, then exposure to mefloquine may or may not account for subsequent symptoms.
The interaction between quinism and OSIs may prove to be quite complex. Consider, for example, recent research on how MDMA, or ecstasy, can help veterans overcome traumatic memories. In a nutshell, a drug that induces feelings of warmth and compassion is paired with a traumatic memory, which helps to settle the anxiety provoked by that memory, with lasting effects.
Is it not possible that quinism does the opposite—a drug that provokes a chronic state of anxiety, when paired with a traumatic event, leads to a greater likelihood of PTSD?
In some tragic circumstances, there may be another source of trauma. Actions taken while under the influence of the drug could lead to horrific moral injuries. I understand that soldiers in the Airborne Regiment in Somalia were given mefloquine. Imagine being such a soldier. You might find yourself asking how you came to violate your values and your duty by acting violently and illegally. Though it may not meet criterion A, perhaps the reaction to the drug is a kind of trauma in itself. Is there anything more traumatic than having your very self, including your values and your sense of reality, stripped away?
Our understanding of quinism is in its infancy. We have yet to grapple with its impact on the diagnosis, misdiagnosis, overlapping diagnosis or exacerbation of operational stress injuries, in part because too few of us are sufficiently aware of the need to screen for mefloquine exposure and subsequent reactions to that exposure.
In our ignorance, we’re also at risk of creating sanctuary traumas. A sanctuary trauma occurs when someone expects to find help and support, but instead experiences invalidation and rejection. Research shows that the experience of such injustice can have a severe impact on recovery from physical and psychological injuries.
Therefore, it’s imperative that the veterans coming forward with stories of quinism have access to well-informed case managers and clinicians, and that means we must disseminate what we know and do the research necessary to learn more, so that we know best how to assess and treat this complex condition.
Certainly, we need to start asking the questions, both as clinicians and researchers. I am grateful that the ministry is taking the questions that need to be asked. I hope that I’ve been of some help to you in that quest.
Thank you for your time.
Conservative
Cathay Wagantall Conservative Yorkton—Melville, SK
Thank you, Chair.
Thank you, Dr. Douglas and Dr. Suter, for being here today. It means a great deal to us to have you both here. You have significant experience that I think is making us very aware that we do need to pursue this further.
On that, the surgeon general's report on mefloquine in conclusion number seven stated, “We did not identify any evidence (that met our inclusion criteria) addressing potential long term adverse effects of mefloquine”; yet in contrast, in 2014 the European Medicines Agency concluded, “There is enough evidence...supporting a causal relationship between mefloquine and the occurrence of long lasting and even persistent neuropsychiatric side effects.”
This to me just shows the need for more research. How do each of you reconcile two such very different reports being presented to us?
Psychologist, Central Ontario Psychology, As an Individual
I know I'm aware of it. I believe that both Australia and the U.K. have identified mefloquine quite positively as a significant risk factor for neuropsychiatric disorders.
I would tend to agree that the research is in its infancy, as I said. Clearly more needs to be done, but I think if we listen to the veterans and the stories that they're telling us, what we learn is that there is this very significant reaction. It's not simply exposure to mefloquine, and perhaps that's the confounding variable here. If you only look at whether the veteran was exposed, then that might wash out in the statistics. If you look at the veterans who have developed that reaction, the initial reaction to taking the mefloquine, that's going to predict the longer term impact. Perhaps that's the piece that has been confusing here.
Conservative
Cathay Wagantall Conservative Yorkton—Melville, SK
It's choosing to home in specifically on those who indicate that they had a severe reaction.
Conservative
Cathay Wagantall Conservative Yorkton—Melville, SK
What about you, Dr. Suter? You've indicated that you've worked with individuals dealing with these issues of visual and brain injuries. What is your take from what you've experienced with the effects of mefloquine?
Optometrist, As an Individual
First of all, I don't believe that there's a very good awareness about mefloquine in my profession. There are a number of neuro-optometrists who have worked with patients with mefloquine toxicity. I have a few cases, but in calling my colleagues in preparation for today, what I found is that the information is disappearing from the records. A lot of the people who we saw, we saw back in 2011 and 2012 in the U.S., and those records are being purged by doctors.
We have not done a good job of getting the visual consequences out into the literature. It's been not a small issue for the people who are involved, but it's a smallish issue in terms of the overall look at brain injury.
Optometrist, As an Individual
Optometry is notoriously poor at getting the research out because we are traditionally a clinical profession, I think, so—
Conservative
Cathay Wagantall Conservative Yorkton—Melville, SK
I just want to ask one more question.
Within the Canadian Armed Forces, mefloquine accounts for less than 5% of malarial prevention prescriptions now. Since June 2017, mefloquine has been recommended only when members requested it themselves. I believe this, to a large extent, is due to the work that we've been able to do to date in Canada to draw better awareness to the impacts of this drug.
It's only used when they request it or when other drugs aren't able to be used. That sounds very good to me, but there's a huge gap in dealing with those who have suffered in the past when they were required to take this drug within Canada.
Dr. Douglas, what would you say to this? This is a new directive for future use but what about other measures in regard to Canadian Armed Forces members and veterans who were required to take it, who are facing injuries, and nothing has been done significantly by anyone to draw their attention to this?
Psychologist, Central Ontario Psychology, As an Individual
I think it's a very significant issue and I think it has a relatively simple solution, which is to reach out to veterans and simply ask them if they have had an anti-malarial drug in the past. Was it a weekly dosage one? That would tend to lean it towards having been mefloquine. Did they have any kind of significant reactions to that drug at the time?
From what I've heard, it's a fairly common reaction. I know the research is estimating that somewhere around 14% of people exposed to mefloquine may have that prodromal reaction.
It may very well be that a fair number of people have been missed. They may not be connecting something like an ongoing psychotic reaction, for example, to military service. It might be helpful for them to receive that information.
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
Thank you, Mr. Chair.
Thank you both for coming.
Dr. Suter, you spoke about the alterations in perceptions that you can get when you have any problem with the brain stem, and I understand something about the neuro-pathways. Are you aware of what the evidence is that there are specific effects on the brain stem by mefloquine that are causing these changes?
Optometrist, As an Individual
The research that I looked at was that there are micro-lesions that do not show up on imaging that can occur with quinolone use.
Truthfully, again, as I said, I was asked to come because I have some cases of mefloquine toxicity in my practice and because I have expertise in the brain stem brain injury, but—
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
I'm sorry to cut you off. I have very little time.
What was the diagnostic criteria to say that these patients had mefloquine toxicity?
Optometrist, As an Individual
They came in previously diagnosed by other doctors. I believe they were mainly diagnosed by the neuro-otologists who saw them prior to their seeing us.
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
Okay. You talked about a cohort of patients or incidents that had happened. You said these records were purged by doctors. Could you clarify that statement?
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
What records were those, again, just so I'm clear?